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A Study to Evaluate Efficacy and Safety of Anakinra in the Treatment of Acute Gouty Arthritis (anaGO)

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ClinicalTrials.gov Identifier: NCT03002974
Recruitment Status : Active, not recruiting
First Posted : December 26, 2016
Last Update Posted : June 29, 2018
Sponsor:
Information provided by (Responsible Party):
Swedish Orphan Biovitrum

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.

Condition or disease Intervention/treatment Phase
Acute Gouty Arthritis Drug: Anakinra 100 mg Drug: Triamcinolone Acetonide 40 mg Drug: Placebo to Anakinra 100 mg Drug: Placebo to Triamcinolone Acetonide 40 mg Phase 2

Detailed Description:
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 of last patient in the study. The extension period for the individual patient in the study will be maximum two years (104 weeks). 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 165 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Gouty Arthritis, Followed by an Extension Period of up to 2 Years
Actual Study Start Date : December 2016
Actual Primary Completion Date : June 2018
Estimated Study Completion Date : September 2019


Arm Intervention/treatment
Experimental: Anakinra 100 mg
1 subcutaneous injection of Anakinra 100 mg once daily for 5 days, 1 subcutaneous injection of Placebo to Anakinra 100 mg once daily for 5 days and 1 single intramuscular injection of Placebo to Triamcinolone Acetonide 40 mg
Drug: Anakinra 100 mg
100 mg/0.67 mL solution in single-use prefilled syringes for subcutaneous injection
Other Name: Kineret

Drug: Placebo to Anakinra 100 mg
sterile solution for injection (0.67 mL) in a single-use prefilled syringe identical to the anakinra syringe
Other Name: Placebo Kineret

Drug: Placebo to Triamcinolone Acetonide 40 mg
1 mL intramuscular injectable suspension with identical appearance as the Triamcinolone Acetonide suspension
Other Name: Placebo Kenalog

Experimental: Anakinra 200 mg
2 subcutaneous injections of Anakinra 100 mg (2 syringes) once daily for 5 days and 1 single intramuscular injection of Placebo to Triamcinolone Acetonide 40 mg
Drug: Anakinra 100 mg
100 mg/0.67 mL solution in single-use prefilled syringes for subcutaneous injection
Other Name: Kineret

Drug: Placebo to Triamcinolone Acetonide 40 mg
1 mL intramuscular injectable suspension with identical appearance as the Triamcinolone Acetonide suspension
Other Name: Placebo Kenalog

Active Comparator: Triamcinolone 40 mg
2 subcutaneous injections of Placebo to Anakinra 100 mg once daily for 5 days and 1 single intramuscular injection of Triamcinolone Acetonide 40 mg
Drug: Triamcinolone Acetonide 40 mg
1 mL intramuscular injection of a 40 mg/mL injectable suspension
Other Names:
  • Kenalog
  • Triamcinolone

Drug: Placebo to Anakinra 100 mg
sterile solution for injection (0.67 mL) in a single-use prefilled syringe identical to the anakinra syringe
Other Name: Placebo Kineret




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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)

  2. 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").

  3. 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)

  4. 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)

  5. 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

  6. 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 ]
  7. 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

  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. The percent of patients with at least one adverse event [ Time Frame: Through study completion, at 12 weeks after last flare treated during the extension period ]
    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.

  15. The percent of patients with at least one Serious Adverse Event, including death [ Time Frame: Through study completion, at 12 weeks after last flare treated during the extension period ]
    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.

  16. 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 during the extension period ]
  17. 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 treated during the extension period ]
    Confirmed ADA positive samples will be analysed for the presence of neutralizing antibodies

  18. Proportion of patients with neutralizing antibodies [ 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 during the extension period ]
    Confirmed ADA positive samples will be analysed for the presence of neutralizing antibodies

  19. Change from baseline in Short Form (36) Health Survey, acute version 2 (SF-36®) physical functioning domain score [ Time Frame: at baseline, Day 8 and Day 15 for the first flare treated in the study ]
    Exploratory objective

  20. Change from baseline in health related quality of life EuroQol 5 dimensions 5 levels (EQ-5D-5L) [ Time Frame: at baseline, Day 8 and Day 15 for the first flare treated in the study ]
    Exploratory objective

  21. Work productivity and activity impairment:specific health problems due to a gouty arthritis flare (WPAI:SHP v.2.0) [ Time Frame: Recorded up to Day 15 for the first flare and subsequent flares treated during the extension period ]
    Exploratory objective

  22. Health care resource utilization due to a gouty arthritis flare [ Time Frame: Recorded up to Day 15 for the first flare and subsequent flares treated during the extension period ]
    Exploratory objective: number of days with hospitalization and un-scheduled outpatient visits



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed Informed consent
  • Patient meeting the American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) 2015 gout classification criteria
  • History of ≥1 self-reported flares of gouty arthritis within 12 months
  • Current ongoing flare of gouty arthritis characterized by pain intensity
  • Currently tender and swollen joint
  • Onset of current flare within 4 days
  • Intolerant, unresponsive, contraindicated or not appropriate for treatment with NSAIDs and colchicine (both treatment options)
  • If on urate-lowering therapy, on a stable dose and regimen
  • Women of childbearing potential willing to use adequate contraception

Inclusion criteria for treatment of subsequent flare(s)

  • Current flare of gouty arthritis characterized by pain intensity
  • Currently tender and swollen joint
  • Women of childbearing potential willing to use adequate contraception

Exclusion Criteria:

  • Use of specified pain relief medications or biologics (including glucocorticoids, narcotics, paracetamol/acetaminophen, NSAIDs, colchicine, IL-blockers and tumor necrosis factor inhibitors) within specified periods prior to randomization
  • Contraindication to triamcinolone
  • Polyarticular gouty arthritis involving more than 4 joints
  • Rheumatoid arthritis, evidence/suspicion of infectious/septic arthritis, or other acute inflammatory arthritis
  • History of malignancy within the past 5 years. Exceptions are basal cell skin cancer, carcinoma-in-situ of the cervix or low-risk prostate cancer after curative therapy.
  • Known hypersensitivity to Escherichia coli-derived proteins, Kineret® (anakinra), Kenalog® (triamcinolone acetonide) or any components of the products.
  • Known presence or suspicion of active or recurrent bacterial, fungal or viral infections, including tuberculosis, or HIV infection or hepatitis B or C infection
  • Presence of severe renal function impairment chronic kidney disease (CKD) stages 4 and 5
  • Presence of neutropenia
  • Uncontrolled clinically significant hematologic, pulmonary, endocrine, metabolic, gastrointestinal, central nervous system or hepatic disease
  • History of myocardial infarction, unstable angina, cerebrovascular events, or coronary artery bypass grafting, New York Heart Association (NYHA) class III or IV heart failure within the previous 3 months
  • Patients who have undergone major surgery within 2 weeks, or have an unhealed operation wound/s
  • Presence of any medical or psychological condition or laboratory result that in the opinion of the investigator might create risk to the patients or to the study.
  • Earlier or current treatment with anakinra
  • Pregnant or lactating women
  • History of >12 flares overall in the 6 months prior to randomization

Exclusion criteria for treatment of subsequent flare(s):

  • Known presence or suspicion of active or recurrent bacterial, fungal or viral infections, including tuberculosis, or HIV infection or hepatitis B or C infection.
  • Presence of severe renal function impairment CKD stages 4 and 5
  • Presence of neutropenia
  • History of myocardial infarction, unstable angina, cerebrovascular events, or coronary artery bypass grafting, NYHA class III or IV heart failure within the previous 3 months
  • Patients who have undergone major surgery within 2 weeks or have an unhealed operation wound/s.
  • Pregnant or lactating women.
  • Presence of any condition or laboratory result that in the opinion of the investigator makes the patient not appropriate for treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03002974


  Show 37 Study Locations
Sponsors and Collaborators
Swedish Orphan Biovitrum
Investigators
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Study Director: Sven Ohlman, MD, PhD Swedish Orphan Biovitrum AB

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Responsible Party: Swedish Orphan Biovitrum
ClinicalTrials.gov Identifier: NCT03002974     History of Changes
Other Study ID Numbers: Sobi.ANAKIN-401
First Posted: December 26, 2016    Key Record Dates
Last Update Posted: June 29, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Swedish Orphan Biovitrum:
Gout
Interleukin 1 receptor antagonist
IL-1 receptor antagonist

Additional relevant MeSH terms:
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Arthritis
Arthritis, Gouty
Joint Diseases
Musculoskeletal Diseases
Gout
Crystal Arthropathies
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Triamcinolone
Triamcinolone Acetonide
Triamcinolone hexacetonide
Triamcinolone diacetate
Interleukin 1 Receptor Antagonist Protein
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents