Safety and Efficacy of Canakinumab Prefilled Syringes in Frequently Flaring Acute Gouty Arthritis Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01356602
First received: May 16, 2011
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

This study assessed the safety and efficacy of canakinumab pre-filled syringes in comparison to triamcinolone acetonide 40 mg and canakinumab lyophilizate in patients that have frequent flares of acute gouty arthritis.


Condition Intervention Phase
Acute Gouty Arthritis
Drug: Canakinumab pre-filled syringe
Drug: Canakinumab lyophilized powder
Drug: Triamcinolone Acetonide
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Active-controlled Study of Canakinumab Prefilled Syringes or Reconstituted Lyophilizate Versus Triamcinolone Acetonide for Treating Acute Gouty Arthritis Flares in Frequently Flaring Patients

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Pain Intensity on a 0-100 mm Visual Analog Scale (VAS) Between the Canakinumab 150 mg PFS and Triamcinolone Acetonide 40 mg Groups [ Time Frame: 72 hours post dose ] [ Designated as safety issue: No ]
    The Visual Analog Scale (VAS) is an instrument used to measure a person's subjective quantitative evaluation of an item such as pain intensity. The VAS contains a continuous line between two end points whereby the respondent places a mark on the line to indicate his or her response. In this study, patients scored their pain intensity in the most affected joint of the gout flare on a 0 100 mm VAS. The scale ranged from 0 (no pain) to 100 (unbearable pain). The scores were measured to the nearest millimeter from the left. Missing pain intensity data at 72 hours was imputed using the Last-Observation-Carried-Forward (LOCF) method.


Secondary Outcome Measures:
  • Pain Intensity on a 0 - 100 mm VAS Between the Canakinumab 150 mg PFS and Canakinumab 150 mg LYO Groups [ Time Frame: 72 hours post dose ] [ Designated as safety issue: No ]
    The Visual Analog Scale (VAS) is an instrument used to measure a person's subjective quantitative evaluation of an item such as pain intensity. The VAS contains a continuous line between two end points whereby the respondent places a mark on the line to indicate his or her response. In this study, patients scored their pain intensity in the most affected joint of the gout flare on a 0 100 mm VAS. The scale ranged from 0 (no pain) to 100 (unbearable pain). The scores were measured to the nearest millimeter from the left. Missing pain intensity data at 72 hours was imputed using the Last-Observation-Carried-Forward (LOCF) method.

  • Patient's Assessment of Pain Intensity on a 0-100mm VAS [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    The Visual Analog Scale (VAS) is an instrument used to measure a person's subjective quantitative evaluation of an item such as pain intensity. The VAS contains a continuous line between two end points whereby the respondent places a mark on the line to indicate his or her response. In this study, patients scored their pain intensity in the most affected joint of the gout flare on a 0 100 mm VAS. The scale ranged from 0 (no pain) to 100 (unbearable pain). The scores were measured to the nearest millimeter from the left. The LOCF method was used to impute post-dose pain intensity VAS measurements up to 14 days.

  • Patient's Assessment of Pain Intensity on a 5-point Likert Scale [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    A Likert scale is a type of scale with a range of responses corresponding to an item such as pain. The respondent selects the best response that indicates the respondent's subjective evaluation of the item. Patients scored their pain intensity in the most affected joint of the gout flare on a 5-point Likert scale (none, mild, moderate, severe, extreme). The scores were measured to the nearest millimeter from the left. The LOCF method was used to impute post-dose pain intensity Likert measurements up to 14 days.

  • Number of Patients With at Least One New Gouty Arthritis Flare After Baseline [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Patients met the definition of a new flare if they had: a flare in a joint, which was not a previously affected joint (at baseline or during the study), or a flare in a joint previously affected (at baseline or during the study) after the previous flare in that joint had resolved completely according to the patient's perception. Patients did NOT meet the criterion of having a new gout flare if they had increasing/renewed gout pain in an affected joint before the flare had resolved completely.

  • Time to the First New Gouty Arthritis Flare [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Patients met the definition of a new flare if they had: a flare in a joint, which was not a previously affected joint (at baseline or during the study), or a flare in a joint previously affected (at baseline or during the study) after the previous flare in that joint had resolved completely according to the patient's perception. Patients did NOT meet the criterion of having a new gout flare if they had increasing/renewed gout pain in an affected joint before the flare had resolved completely. Less than 50% of patients had new flares. Therefore, the median time to new flare could not be calculated.

  • Time to 50% Reduction in Baseline Pain on a 0 - 100 VAS [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    The Visual Analog Scale (VAS) is an instrument used to measure a person's subjective quantitative evaluation of an item such as pain intensity. The VAS contains a continuous line between two end points whereby the respondent places a mark on the line to indicate his or her response. In this study, patients scored their pain intensity in the most affected joint of the gout flare on a 0 100 mm VAS. The scale ranged from 0 (no pain) to 100 (unbearable pain). The scores were measured to the nearest millimeter from the left. Kaplan Meier estimate of time to 50% reduction in baseline pain, along with associated 95% confidence interval, were reported.

  • Time to Resolution of Gouty Arthritis Flare as Reported by Patient [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    Patients completed diary entries at 6, 12, 24, 48 and 72 hours post dose and then daily up to 7 days post-dose and/or daily until resolution of the flare. Kaplan Meier estimate of time to resolution of gouty flare as reported by patient, along with associated 95% confiedence interval, were reported.

  • Patient's Global Assessment of Response to Treatment on a 5-point Likert Scale [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    A Likert scale is a type of scale with a range of responses corresponding to an item such as pain. The respondent selects the best response that indicates the respondent's subjective evaluation of the item. Patients scored their response to treatment on a 5-point Likert scale (excellent, good, acceptable, slight, poor). This outcome measure shows the number of patients indicating each score on the scale.

  • Physician's Global Assessment of Response to Treatment on a 5 Point Likert Scale [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    A Likert scale is a type of scale with a range of responses corresponding to an item such as pain. The respondent selects the best response that indicates the respondent's subjective evaluation of the item. Study physicians scored their assessment of the patients' response to treatment on a 5-point Likert scale (very good, good, fair, poor, very poor).

  • Physician's Assessment of Tenderness [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    The study physician assessed the most affected joint for tenderness. Tenderness was measured on a 0 - 3 point scale as follows: 0 = no pain, 1 = patient states that "there is pain", 2 = patient states "there is pain and winces" and 3 = patient states "there is pain, winces and withdraws" on palpation or passive movement of the affected study joint.

  • Physician's Assessment of Swelling [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    The study physician assessed the most affected joint for swelling. Swelling was measured on a 0 - 3 point scale as follows: 0 = no swelling, 1 = palpable, 2= visible and 3 = bulging beyond the joint margins.

  • Physician's Assessment of Erythema [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    The study physician assessed the most affected joint for erythema. Erythema was assessed as present, absent or not assessable.

  • Physician's Assessment of Range of Motion of the Most Affected Joint [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    The study physician assessed the patient's range of motion of the most affected joint on a 5 point Likert scale (normal, mildly restricted, moderately restricted, severely restricted and immobilized).

  • Proportion of Patients With Rescue Medication Intake [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Patients used a diary to record the time of intake of rescue medication and the amount taken.

  • Time to First Rescue Medication Intake [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    Patients used a diary to record the time of intake of rescue medication and the amount taken.

  • Amount of Rescue Medication Taken (mg) [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    Patients used a diary to record the time of intake of rescue medication and the amount taken.

  • C-reactive Protein Level [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    A central laboratory was used for analysis of all blood samples collected.


Enrollment: 397
Study Start Date: May 2011
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Canakinumab, pre-filled syringes (PFS)
Patients on this arm received 150 mg subcutaneously (s.c.) at randomization and upon new flare. The doses were provided as pre-filled syringes. The patients were given 3 injections: two placebo and one active drug.
Drug: Canakinumab pre-filled syringe
Canakinumab pre-filled syringe
Drug: Placebo
Matching placebo to Canakinumab (PFS), Canakinumab (LYO) and Triamcinolone Acetonide
Active Comparator: Canakinumab, lyophilizate (LYO)
The patients on this arm received 150 mg s.c. at randomization and upon new flare. The doses were provided as lyophilized powder and had to be reconstituted with water for injection before application. The patients were given 3 injections: two placebo and one active drug.
Drug: Canakinumab lyophilized powder
Canakinumab lyophilized powder
Drug: Placebo
Matching placebo to Canakinumab (PFS), Canakinumab (LYO) and Triamcinolone Acetonide
Active Comparator: Triamcinolone Acetonide
The patients on this arm received 40 mg intramuscular (i.m.) at randomization and upon new flare. The patients were given 3 injections: two placebo and one active drug.
Drug: Triamcinolone Acetonide
Triamcinolone Acetonide
Drug: Placebo
Matching placebo to Canakinumab (PFS), Canakinumab (LYO) and Triamcinolone Acetonide

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • 3 or more gout flares within last year
  • Contraindication, intolerance or lack of efficacy for NSAIDs and/or colchicine
  • Body mass index of less than or equal to 45 kg/m2

Exclusion criteria:

  • Use of the following therapies (within varying protocol defined timeframes): corticosteroids, narcotics, topical ice/cold packs, chronic opiate treatment, NSAIDs (such as aspirin), colchicine.
  • Hemodialysis
  • Live vaccine within 3 months before first dose
  • Donation or loss of 400 mL or more within 3 months before first dose
  • Gout brought on by other factors such as chemotherapy, lead, transplant, etc.
  • Presence of other acute inflammatory arthritis such as Rheumatoid Arthritis
  • Any conditions or significant medical problems that puts the patient at an unacceptable immunological risk to receive this type of therapy such as HIV, Hepatitis, Tuberculosis and other infections/conditions
  • Significant cardiovascular conditions such as uncontrolled hypertension
  • Significant medical diseases such as uncontrolled diabetes, thyroid disease
  • History of malignancy of any organ system within the past 5 years
  • Women who are pregnant or nursing
  • Other protocol-defined inclusion/exclusion criteria may apply
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01356602

  Show 99 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01356602     History of Changes
Other Study ID Numbers: CACZ885H2361, 2010-024173-39
Study First Received: May 16, 2011
Results First Received: September 6, 2013
Last Updated: December 10, 2013
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices
Hungary: Institutional Ethics Committee
Lithuania: State Medicine Control Agency - Ministry of Health

Keywords provided by Novartis:
Gout
arthritis
gout flare
acute gout
gouty
rheumatic disease
uric acid

Additional relevant MeSH terms:
Arthritis
Arthritis, Gouty
Joint Diseases
Musculoskeletal Diseases
Gout
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Triamcinolone hexacetonide
Triamcinolone
Triamcinolone Acetonide
Antibodies, Monoclonal
Triamcinolone diacetate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014