Clinical Trial: A Study to Evaluate Efficacy and Safety of Anakinra in the Treatment of Acute Gouty Arthritis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Randomized, Double-blind, Active-control, Multicenter, Efficacy and Safety Study of 2 Dose Levels of Subcutaneous Anakinra Compared to Intramuscular Triamcinolone in the Treatment of Acute

Brief Summary: The purpose of this study is to evaluate how anakinra relieves pain for patients with acute gout that cannot take non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine. The patients will be divided in different treatment groups to compare anakinra to the available drug triamcinolone.

Detailed Summary: Patients will be randomized to treatment at their first gout flare in the study. The first treatment period will be followed by an extension period during which the patients will receive the same treatment for any subsequent flares within 52 weeks of randomization. Each new flare treated will initiate a new series of study visits and assessments according to specified schedule of events. Only if a patient experience a new flare after Day 15 of the latest flare they can start a new treatment period. The comparison of primary interest is between anakinra (100 mg and 200 mg combined) and 40 mg triamcinolone, and as a secondary objective the 2 different doses of anakinra will be evaluated as well as assessment for subsequent flares.
Sponsor: Swedish Orphan Biovitrum

Current Primary Outcome: Change in patient-assessed pain intensity in the index joint from baseline to 24-72 hours for the first gout flare treated in the study as measured by VAS [ Time Frame: At baseline (pre-dose) and at 6, 12, 18, 24, 48 and 72 hours for the first gout flare treated in the study ]

Patients will score their pain intensity in the joint most affected at baseline (index joint) on a 0-100 mm visual analogue scale (VAS), ranging from no pain (0) to unbearable pain (100). Average of the assessments performed at 24, 48 and 72 hours.


Original Primary Outcome: Change in patient-assessed pain intensity in the index joint from baseline to 24-72 hours for the first gout flare treated in the study as measured by VAS [ Time Frame: From baseline (pre-dose) and at baseline, 6, 12, 18, 24, 48 and 72 hours for the first gout flare treated in the study ]

Patients will score their pain intensity in the joint most affected at baseline (index joint) on a 0-100 mm visual analogue scale (VAS), ranging from no pain (0) to unbearable pain (100). Average of the assessments performed at 24, 48 and 72 hours.


Current Secondary Outcome:

  • Change in patient-assessed pain intensity in the index joint from baseline at time points from 6 hours to 8 days for the first gout flare treated in the study as measured by VAS [ Time Frame: At baseline (pre-dose) and at 6, 12, 18, 24, 36, 48 and 72 hours and Day 5, 6, 7 and 8 for the first gout flare treated in the study ]
    Patients will score their pain intensity in the joint most affected at baseline (index joint) on a 0-100 mm visual analogue scale (VAS), ranging from no pain (0) to unbearable pain (100)
  • Change in patient-assessed pain intensity in the index joint from baseline at time points from 6 hours to 8 days for the first gout flare treated in the study as measured by 5-point Likert scale [ Time Frame: At baseline (pre-dose) and at 6, 12, 18, 24, 36, 48 and 72 hours and Day 5, 6, 7 and 8 for the first gout flare treated in the study ]
    Patients will score their pain intensity in the joint most affected at baseline (index joint) on a 5-point Likert scale (0-4 point scale: "none", "mild", "moderate", "severe", "extreme").
  • Time to onset of effect [ Time Frame: From baseline (predose) up to Day15 of the first flare treated in the study ]
    Onset of effect defined as 20% change from baseline pain intensity in the index joint on a visual analogue scale (VAS)
  • Time to response [ Time Frame: From baseline (predose) up to Day15 of the first flare treated in the study ]
    Response defined as 50% change from baseline pain intensity on a visual analogue scale (VAS)
  • Time to resolution of pain [ Time Frame: From baseline (predose) up to Day15 of the first flare ]
    Resolution of pain defined as <10 mm on VAS in the index joint
  • Time to first intake of rescue medication from first investigational drug administration [ Time Frame: From Day 1 to Day 15 for the first flare treated in the study ]
  • Physician's assessment of global response to treatment [ Time Frame: At 72 hours, Day 8 and Day 15 for the first flare treated in the study ]
    5-point Likert scale
  • Physician's assessment of clinical signs in index joint: tenderness [ Time Frame: at 72 hours, Day 8 and Day 15 for the first flare treated in the study ]
  • Physician's assessment of clinical signs in index joint: swelling [ Time Frame: at 72 hours, Day 8 and Day 15 for the first flare treated in the study ]
  • Physician's assessment of clinical signs in index joint: erythema [ Time Frame: at 72 hours, Day 8 and Day 15 for the first flare treated in the study ]
  • Patient´s assessment of global response to treatment (5-point Likert scale) [ Time Frame: at 72 hours, Day 8 and Day 15 for the first flare treated in the study ]
  • Change from baseline in the inflammatory biomarker C reactive protein [ Time Frame: baseline (predose) and at 72 hours, Day 8 and Day 15 for the first flare treated in the study ]
  • Change from baseline in the inflammatory biomarker Serum amyloid A [ Time Frame: baseline (predose) and at 72 hours, Day 8 and Day 15 for the first flare treated in the study ]
  • The percent of patients with at least one adverse event [ Time Frame: Through study completion, at 12 weeks after last flare starting within 52 weeks of randomisation ]
    All adverse events to be recorded Day 1 - Day 28 for each flare. Serious adverse events (SAE) will be collected from informed consent until week 12 for each flare. Any SAE with suspected causal relationship should be reported irrespective of the time of occurrence.
  • The percent of patients with at least one Serious Adverse Event, including death [ Time Frame: Through study completion, at 12 weeks after last flare starting within 52 weeks of randomisation ]
    Serious Adverse Events (SAE) will be collected from informed consent until week 12 for each flare. Any SAE with suspected causal relationship should be reported irrespective of the time of occurrence.
  • Serum concentration of endogenous interleukin-1 receptor antagonist /anakinra [ Time Frame: Baseline (predose) and at 72 hours, Day 8, Day 15, Day 28 and Week 12 for the first flare and subsequent flares treated within 52 weeks of randomization ]
  • Proportion of patients with anti-drug antibodies (ADA) against anakinra [ Time Frame: Baseline (predose) and at 72 hours, Day 8, Day 15, Day 28 and Week 12 for the first flare and subsequent flares treated within 52 weeks of randomization ]
    Confirmed ADA positive samples will be analysed for the presence of neutralizing antibodies
  • Proportion of patients with neutralizing antibodies [ Time Frame: Baseline (predose) and at 72 hours

    Original Secondary Outcome:

    • Change in patient-assessed pain intensity in the index joint from baseline at time points from 6 hours to 8 days for the first gout flare treated in the study as measured by VAS [ Time Frame: At baseline (pre-dose) and at 6, 12, 18, 24, 36, 48 and 72 hours and Day 5, 6, 7 and 8 for the first gout flare treated in the study ]
      Patients will score their pain intensity in the joint most affected at baseline (index joint) on a 0-100 mm visual analogue scale (VAS), ranging from no pain (0) to unbearable pain (100)
    • Change in patient-assessed pain intensity in the index joint from baseline at time points from 6 hours to 8 days for the first gout flare treated in the study as measured by 5-point Likert scale [ Time Frame: At baseline (pre-dose) and at 6, 12, 18, 24, 36, 48 and 72 hours and Day 5, 6, 7 and 8 for the first gout flare treated in the study ]
      Patients will score their pain intensity in the joint most affected at baseline (index joint) on a 5-point Likert scale (0-4 point scale: "none", "mild", "moderate", "severe", "extreme").
    • Time to onset of effect [ Time Frame: From baseline (predose) up to Day15 of the first flare treated in the study ]
      Onset of effect defined as 20% change from baseline pain intensity in the index joint on a visual analogue scale (VAS)
    • Time to response [ Time Frame: From baseline (predose) up to Day15 of the first flare treated in the study ]
      Response defined as 50% change from baseline pain intensity on a visual analogue scale (VAS)
    • Time to resolution of pain [ Time Frame: From baseline (predose) up to Day15 of the first flare ]
      Resolution of pain defined as <10 mm on VAS in the index joint
    • Time to first intake of rescue medication from first investigational drug administration [ Time Frame: From Day 1 to Day 15 for the first flare treated in the study ]
    • Physician's assessment of global response to treatment [ Time Frame: At 72 hours, Day 8 and Day 15 for the first flare treated in the study ]
      5-point Likert scale
    • Physician's assessment of clinical signs in index joint: tenderness [ Time Frame: at 72 hours, Day 8 and Day 15 for the first flare treated in the study ]
    • Physician's assessment of clinical signs in index joint: swelling [ Time Frame: at 72 hours, Day 8 and Day 15 for the first flare treated in the study ]
    • Physician's assessment of clinical signs in index joint: erythema [ Time Frame: at 72 hours, Day 8 and Day 15 for the first flare treated in the study ]
    • Patient´s assessment of global response to treatment (5-point Likert scale) [ Time Frame: at 72 hours, Day 8 and Day 15 for the first flare treated in the study ]
    • Change from baseline in the inflammatory biomarker C reactive protein [ Time Frame: baseline (predose) and at 72 hours, Day 8 and Day 15 for the first flare treated in the study ]
    • Change from baseline in the inflammatory biomarker Serum amyloid A [ Time Frame: baseline (predose) and at 72 hours, Day 8 and Day 15 for the first flare treated in the study ]
    • The percent of patients with at least one adverse event [ Time Frame: Through study completion, at 12 weeks after last flare starting within 52 weeks of randomisation ]
      All adverse events to be recorded Day 1 - week 5 for each flare. Serious adverse events (SAE) will be collected from informed consent until week 12 for each flare. Any SAE with suspected causal relationship should be reported irrespective of the time of occurrence.
    • The percent of patients with at least one Serious Adverse Event, including death [ Time Frame: Through study completion, at 12 weeks after last flare starting within 52 weeks of randomisation ]
      Serious Adverse Events (SAE) will be collected from informed consent until week 12 for each flare. Any SAE with suspected causal relationship should be reported irrespective of the time of occurrence.
    • Serum concentration of endogenous interleukin-1 receptor antagonist /anakinra [ Time Frame: Baseline (predose) and at 72 hours, Day 8, Day 15 and Week 12 for the first flare and subsequent flares treated within 52 weeks of randomization ]
    • Proportion of patients with anti-drug antibodies (ADA) against anakinra [ Time Frame: Baseline (predose) and at 72 hours, Day 8, Day 15 and Week 12 for the first flare and subsequent flares treated within 52 weeks of randomization ]
      Confirmed ADA positive samples will be analysed for the presence of neutralizing antibodies
    • Proportion of patients with neutralizing antibodies [ Time Frame: Baseline (predose) and at 72 hours, Day 8, Day 15

      Information By: Swedish Orphan Biovitrum

      Dates:
      Date Received: December 13, 2016
      Date Started: December 2016
      Date Completion: October 2018
      Last Updated: January 25, 2017
      Last Verified: January 2017