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Study of KRYSTEXXA® (Pegloticase) Plus Methotrexate in Participants With Uncontrolled Gout (MIRROR RCT)

Primary Purpose

Gout

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Pegloticase
methotrexate
placebo
folic acid
gout flare prophylaxis regimen
fexofenadine
acetaminophen
methylprednisolone
Sponsored by
Horizon Therapeutics Ireland DAC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gout focused on measuring gout, uncontrolled gout

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Willing and able to give informed consent.
  2. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the study.
  3. Adult men or women ≥18 years of age.
  4. Uncontrolled gout, defined as meeting the following criteria:

    • Hyperuricemia during the screening period defined as sUA ≥7 mg/dL, and;
    • Failure to maintain normalization of sUA with xanthine oxidase inhibitors at the maximum medically appropriate dose, or with a contraindication to xanthine oxidase inhibitor therapy based on medical record review or subject interview, and;
    • Symptoms of gout including at least 1 of the following:

      • Presence of at least one tophus
      • Recurrent flares defined as 2 or more flares in the past 12 months prior to screening
      • Presence of chronic gouty arthritis
  5. Willing to discontinue any oral urate lowering therapy for at least 7 days prior to MTX dosing at Week -6 and remain off when receiving pegloticase infusions.
  6. Women of childbearing potential (including those with an onset of menopause <2 years prior to screening, non-therapy-induced amenorrhea for <12 months prior to screening, or not surgically sterile [absence of ovaries and/or uterus]) must have negative serum/urine pregnancy tests during Screening and Week -6; subjects must agree to use 2 reliable forms of contraception during the study, one of which is recommended to be hormonal, such as an oral contraceptive. Hormonal contraception must be started ≥1 full cycle prior to Week -6 (start of MTX) and continue for 30 days after the last dose of pegloticase, or at least one ovulatory cycle after the last dose of MTX or placebo for MTX (whichever is the longest duration after the last dose of pegloticase or MTX or placebo for MTX). Highly effective contraceptive methods (with a failure rate <1% per year), when used consistently and correctly, include implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence, or vasectomized partner.
  7. Men who are not vasectomized must agree to use appropriate contraception so as to not impregnate a female partner of reproductive potential during the study, beginning with the initiation of MTX at Week -6 and continuing and for at least 3 months after the last dose of MTX or placebo for MTX.
  8. Able to tolerate MTX 15 mg orally for 2 weeks (Week -6 through Week -4) prior to randomization.

Exclusion Criteria:

  1. Weight >160 kg (352 pounds) at Screening.
  2. Any serious acute bacterial infection, unless treated and completely resolved with antibiotics at least 2 weeks prior to the Week -6 Visit.
  3. Severe chronic or recurrent bacterial infections, such as recurrent pneumonia or chronic bronchiectasis.
  4. Current or chronic treatment with systemic immunosuppressive agents such as MTX, azathioprine, or mycophenolate mofetil; prednisone ≥10 mg/day or equivalent dose of other corticosteroid on a chronic basis (3 months or longer) would also meet exclusion criteria.
  5. History of any transplant surgery requiring maintenance immunosuppressive therapy.
  6. Known history of hepatitis B virus surface antigen positivity or hepatitis B DNA positivity.
  7. Known history of hepatitis C virus ribonucleic acid (RNA) positivity.
  8. Known history of Human Immunodeficiency Virus (HIV) positivity.
  9. Glucose-6-phosphate dehydrogenase deficiency (tested at the Screening Visit).
  10. Chronic renal impairment defined as estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73 m^2 or currently on dialysis.
  11. Non-compensated congestive heart failure or hospitalization for congestive heart failure within 3 months of the Screening Visit, uncontrolled arrhythmia, treatment for acute coronary syndrome (myocardial infarction or unstable angina), or uncontrolled blood pressure (>160/100 mmHg) prior to Randomization at Week -4.
  12. Pregnant, planning to become pregnant, breastfeeding, planning to impregnate female partner, or not on an effective form of birth control, as determined by the Investigator.
  13. Prior treatment with pegloticase, another recombinant uricase (rasburicase), or concomitant therapy with a polyethylene glycol-conjugated drug.
  14. Known allergy to pegylated products or history of anaphylactic reaction to a recombinant protein or porcine product.
  15. Contraindication to MTX treatment or MTX treatment considered inappropriate.
  16. Known intolerance to MTX.
  17. Receipt of an investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to MTX administration at Week -6 or plans to take an investigational drug during the study.
  18. Liver transaminase levels (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) > upper limit of normal (ULN) or albumin < the lower limit of normal (LLN) at the Screening Visit).
  19. Chronic liver disease.
  20. White blood cell count < 4,000/µL, hematocrit < 32 percent, or platelet count < 75,000/µL.
  21. Currently receiving systemic or radiologic treatment for ongoing cancer.
  22. History of malignancy within 5 years other than non-melanoma skin cancer or in situ carcinoma of cervix.
  23. Diagnosis of osteomyelitis.
  24. Known history of hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome.
  25. Unsuitable candidate for the study, based on the opinion of the Investigator (e.g., cognitive impairment), such that participation might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements or complete the study.
  26. Alcohol use in excess of 3 alcoholic beverages per week.
  27. A known intolerance to all protocol standard gout flare prophylaxis regimens (i.e. subject must be able to tolerate at least one: colchicine and/or non-steroidal anti inflammatory drugs and/or low dose prednisone ≤10 mg/day).
  28. Current pulmonary fibrosis, bronchiectasis or interstitial pneumonitis. If deemed necessary by the Investigator, a chest X-ray may be performed during Screening.

Sites / Locations

  • University of Alabama
  • Orthopedic Physicians Alaska
  • Arizona Arthritis and Rheumatology Research, PLLC - Flagstaff
  • Arizona Arthritis and Rheumatology Research, PLLC-West
  • Arizona Arthritis and Rheumatology Research, PLLC-East
  • Applied Research Center of Arkansas, Inc
  • TriWest Research Associates
  • Advanced Investigative Medicine, Inc.
  • Axis Clinical Trials
  • ACRC Studies
  • ClinEdge Sierra Rheumatology, Inc.
  • East Bay Rheumatology Medical Group, Inc.
  • Providence St. John's Health Clinic
  • Medvin Clinical Research
  • San Fernando Valley Health Institute
  • Ventura Clinical Trials
  • University of Colorado Division of Rheumatology
  • Denver Arthritis Clinic
  • Avail Clinical Research
  • Prohealth Research Center
  • Omega Research Maitland
  • DMI Research
  • Napa Research Center
  • GCP Clinical Research
  • Florida Medical Clinic, LLC
  • St. Luke's Clinic - Rheumatology
  • MD Medical Research
  • The Center for Rheumatology and Bone Research
  • Infusion Associates
  • Clinical Research Institute of Michigan, LLC
  • Benefis Hospital
  • Physician Research Collaboration, LLC
  • Santa Fe Rheumatology
  • Long Island Arthritis & Osteoporosis Care
  • Buffalo Rheumatology and Medicine
  • NorthEast Rheumatology/Atrium Health
  • NorthEast Rheumatology
  • Medication Management, LLC
  • ClinEdge PMG Research of Hickory, LLC
  • ClinEdge PMG Research of Salisbury, LLC
  • Shelby Clinical Research, LLC
  • PMG Research of Wilmington, LLC
  • Premier Clinical/STAT Research
  • Paramount Medical Research & Consulting, LLC
  • Clinical Research Source Inc.
  • Premier Clinical/STAT Research - Springboro
  • Altoona Center for Clinical Research
  • Piedmont Arthritis Clinic
  • Articularis Healthcare Group
  • West Tennessee Research Institute
  • Ramesh C. Gupta, M.D.
  • Diagnostic and Interventional Nephrology Of Houston
  • Research Consultants - Frostwood
  • Research Consultants - Astoria
  • Arthritis Clinic of Central Texas
  • Arthritis & Osteoporosis Clinic - Waco
  • Clear Lake Specialties
  • Western Washington Arthritis Clinic
  • Arthritis Northwest
  • Rheumatic Disease Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Pegloticase + MTX

Pegloticase + Placebo

Arm Description

Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + Immunomodulator (IMM) Period, in addition to oral 15 mg MTX, participants receive intravenous (IV) pegloticase 8 mg administered every 2 weeks (Q2W) for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for infusion reaction (IR) prophylaxis.

Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral placebo for MTX weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + IMM Period, in addition to oral placebo for MTX, all participants receive IV pegloticase 8 mg administered Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.

Outcomes

Primary Outcome Measures

Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6
Responders are defined as participants achieving and maintaining sUA < 6 mg/dL for at least 80% of the time during Month 6. Month 6 includes pre- and post-infusion sUA assessments at Weeks 20 and 22, non-infusion sUA at Weeks 21 and 23, pre-infusion sUA at Week 24 and any unscheduled sUA between Week 20 and Week 24. A participant must have had ≥ 2 sUA observations from different visits in order to be eligible as a responder. Participants meeting the stopping rule (those with a pre-infusion sUA >6 mg/dL at 2 consecutive scheduled trial visits beginning with the Week 2 Visit stopped pegloticase dosing) were counted as non-responders.

Secondary Outcome Measures

Percentage of sUA (sUA < 6 mg/dL) Responders During Month 12
Responders are defined as participants achieving and maintaining sUA <6 mg/dL for at least 80% of the time during Month 12 (Weeks 48, 50 and 52). Month 12 includes pre- and post-infusion sUA Weeks 48 and 50, pre-infusion sUA at Week 52, and any unscheduled sUA assessments done at unscheduled visits between Week 48 and 52. A participant must have had ≥ 2 sUA observations from different visits in order to be eligible as a responder. Participants meeting the stopping rule (those with a pre-infusion sUA >6 mg/dL at 2 consecutive scheduled trial visits beginning with the Week 2 Visit stopped pegloticase dosing) were counted as non-responders.
Percentage of Participants With Complete Resolution of ≥ 1 Tophi at Week 52
Percentage of participants with complete resolution of ≥ 1 tophi (using digital photography) at Week 52 in participants with tophi at baseline. Participants with resolution of ≥ 1 tophi at a visit are participants with resolution of ≥ 1 tophi at the visit (i.e. have complete response), and no progressive disease for any other tophi.
Mean Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52
HAQ-DI is a self-report functional status instrument that is filled out by the participant and measures disability over the past week via 20 questions relating to 8 domains of function: dressing, grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. The HAQ-DI ranges from 0 to 3 with higher values indicating higher disability. A change from baseline value of 0 is imputed at the first post-baseline visit for any participants without post-baseline values.
Mean Change From Baseline HAQ Pain Score at Week 52
The HAQ-Pain score rates the participant's pain over the past week from 0 to 100 with 0 = no pain and 100 = severe pain. A change from baseline value of 0 is imputed at the first post-baseline visit for any participants without post-baseline values.
Mean Change From Baseline in HAQ Health Score at Week 52
The HAQ health scale is a self-reported measure of overall health. Participants are asked to rate how they are doing, considering all the ways arthritis affects them, on a scale of 0 to 100, where 0 represents very well and 100 represents very poor. A change from baseline value of 0 is imputed at the first post-baseline visit for any participants without post-baseline values.

Full Information

First Posted
June 19, 2019
Last Updated
February 21, 2023
Sponsor
Horizon Therapeutics Ireland DAC
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1. Study Identification

Unique Protocol Identification Number
NCT03994731
Brief Title
Study of KRYSTEXXA® (Pegloticase) Plus Methotrexate in Participants With Uncontrolled Gout
Acronym
MIRROR RCT
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled Gout Receiving KRYSTEXXA® (Pegloticase) (MIRROR Randomized Controlled Trial [RCT])
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
June 13, 2019 (Actual)
Primary Completion Date
March 17, 2021 (Actual)
Study Completion Date
April 11, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Horizon Therapeutics Ireland DAC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to assess the potential for pegloticase with methotrexate (MTX) to increase the response rate seen with pegloticase alone, and to characterize the safety, tolerability and pharmacokinetics (PK) of the concomitant use of pegloticase with MTX, by comparing pegloticase co-administered with MTX to pegloticase co-administered with placebo for MTX in adults with uncontrolled gout.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gout
Keywords
gout, uncontrolled gout

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
152 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pegloticase + MTX
Arm Type
Experimental
Arm Description
Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + Immunomodulator (IMM) Period, in addition to oral 15 mg MTX, participants receive intravenous (IV) pegloticase 8 mg administered every 2 weeks (Q2W) for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for infusion reaction (IR) prophylaxis.
Arm Title
Pegloticase + Placebo
Arm Type
Placebo Comparator
Arm Description
Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral placebo for MTX weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + IMM Period, in addition to oral placebo for MTX, all participants receive IV pegloticase 8 mg administered Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.
Intervention Type
Biological
Intervention Name(s)
Pegloticase
Other Intervention Name(s)
KRYSTEXXA®
Intervention Description
IV pegloticase 8 mg Q2W
Intervention Type
Drug
Intervention Name(s)
methotrexate
Other Intervention Name(s)
MTX
Intervention Description
Oral MTX 15 mg weekly
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Oral placebo for MTX
Intervention Type
Dietary Supplement
Intervention Name(s)
folic acid
Intervention Description
Folic acid 1 mg orally every day beginning at Week -6 until prior to the Week 52 Visit.
Intervention Type
Drug
Intervention Name(s)
gout flare prophylaxis regimen
Intervention Description
Prior to beginning the Pegloticase + IMM Period, participants must have been taking at least 1 protocol-standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day) for ≥ 1 week before the first dose of pegloticase and to continue flare prophylaxis per American College of Rheumatology guidelines [Khanna D et al. 2012] for the greater of 1) 6 months, 2) 3 months after achieving target serum urate (sUA < 6 mg/dL) for participants with no tophi detected on physical exam, or 3) 6 months after achieving target serum urate (sUA < 5 mg/dL) for participants with one or more tophi detected on initial physical exam that then resolved.
Intervention Type
Drug
Intervention Name(s)
fexofenadine
Intervention Description
For IR prophylaxis, fexofenadine (180 mg orally) taken the day before each infusion and on the morning of each infusion.
Intervention Type
Drug
Intervention Name(s)
acetaminophen
Intervention Description
For IR prophylaxis, acetaminophen (1000 mg orally) taken the morning of each infusion.
Intervention Type
Drug
Intervention Name(s)
methylprednisolone
Intervention Description
For IR prophylaxis, methylprednisolone (125 mg IV) given over an infusion duration between 10 - 30 minutes, immediately prior to each infusion.
Primary Outcome Measure Information:
Title
Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6
Description
Responders are defined as participants achieving and maintaining sUA < 6 mg/dL for at least 80% of the time during Month 6. Month 6 includes pre- and post-infusion sUA assessments at Weeks 20 and 22, non-infusion sUA at Weeks 21 and 23, pre-infusion sUA at Week 24 and any unscheduled sUA between Week 20 and Week 24. A participant must have had ≥ 2 sUA observations from different visits in order to be eligible as a responder. Participants meeting the stopping rule (those with a pre-infusion sUA >6 mg/dL at 2 consecutive scheduled trial visits beginning with the Week 2 Visit stopped pegloticase dosing) were counted as non-responders.
Time Frame
Month 6 (Weeks 20, 21, 22, 23 and 24)
Secondary Outcome Measure Information:
Title
Percentage of sUA (sUA < 6 mg/dL) Responders During Month 12
Description
Responders are defined as participants achieving and maintaining sUA <6 mg/dL for at least 80% of the time during Month 12 (Weeks 48, 50 and 52). Month 12 includes pre- and post-infusion sUA Weeks 48 and 50, pre-infusion sUA at Week 52, and any unscheduled sUA assessments done at unscheduled visits between Week 48 and 52. A participant must have had ≥ 2 sUA observations from different visits in order to be eligible as a responder. Participants meeting the stopping rule (those with a pre-infusion sUA >6 mg/dL at 2 consecutive scheduled trial visits beginning with the Week 2 Visit stopped pegloticase dosing) were counted as non-responders.
Time Frame
Month 12 (Weeks 48, 50 and 52)
Title
Percentage of Participants With Complete Resolution of ≥ 1 Tophi at Week 52
Description
Percentage of participants with complete resolution of ≥ 1 tophi (using digital photography) at Week 52 in participants with tophi at baseline. Participants with resolution of ≥ 1 tophi at a visit are participants with resolution of ≥ 1 tophi at the visit (i.e. have complete response), and no progressive disease for any other tophi.
Time Frame
Baseline, Week 52
Title
Mean Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52
Description
HAQ-DI is a self-report functional status instrument that is filled out by the participant and measures disability over the past week via 20 questions relating to 8 domains of function: dressing, grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. The HAQ-DI ranges from 0 to 3 with higher values indicating higher disability. A change from baseline value of 0 is imputed at the first post-baseline visit for any participants without post-baseline values.
Time Frame
Baseline, Week 52
Title
Mean Change From Baseline HAQ Pain Score at Week 52
Description
The HAQ-Pain score rates the participant's pain over the past week from 0 to 100 with 0 = no pain and 100 = severe pain. A change from baseline value of 0 is imputed at the first post-baseline visit for any participants without post-baseline values.
Time Frame
Baseline, Week 52
Title
Mean Change From Baseline in HAQ Health Score at Week 52
Description
The HAQ health scale is a self-reported measure of overall health. Participants are asked to rate how they are doing, considering all the ways arthritis affects them, on a scale of 0 to 100, where 0 represents very well and 100 represents very poor. A change from baseline value of 0 is imputed at the first post-baseline visit for any participants without post-baseline values.
Time Frame
Baseline, Week 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Willing and able to give informed consent. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the study. Adult men or women ≥18 years of age. Uncontrolled gout, defined as meeting the following criteria: Hyperuricemia during the screening period defined as sUA ≥7 mg/dL, and; Failure to maintain normalization of sUA with xanthine oxidase inhibitors at the maximum medically appropriate dose, or with a contraindication to xanthine oxidase inhibitor therapy based on medical record review or subject interview, and; Symptoms of gout including at least 1 of the following: Presence of at least one tophus Recurrent flares defined as 2 or more flares in the past 12 months prior to screening Presence of chronic gouty arthritis Willing to discontinue any oral urate lowering therapy for at least 7 days prior to MTX dosing at Week -6 and remain off when receiving pegloticase infusions. Women of childbearing potential (including those with an onset of menopause <2 years prior to screening, non-therapy-induced amenorrhea for <12 months prior to screening, or not surgically sterile [absence of ovaries and/or uterus]) must have negative serum/urine pregnancy tests during Screening and Week -6; subjects must agree to use 2 reliable forms of contraception during the study, one of which is recommended to be hormonal, such as an oral contraceptive. Hormonal contraception must be started ≥1 full cycle prior to Week -6 (start of MTX) and continue for 30 days after the last dose of pegloticase, or at least one ovulatory cycle after the last dose of MTX or placebo for MTX (whichever is the longest duration after the last dose of pegloticase or MTX or placebo for MTX). Highly effective contraceptive methods (with a failure rate <1% per year), when used consistently and correctly, include implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence, or vasectomized partner. Men who are not vasectomized must agree to use appropriate contraception so as to not impregnate a female partner of reproductive potential during the study, beginning with the initiation of MTX at Week -6 and continuing and for at least 3 months after the last dose of MTX or placebo for MTX. Able to tolerate MTX 15 mg orally for 2 weeks (Week -6 through Week -4) prior to randomization. Exclusion Criteria: Weight >160 kg (352 pounds) at Screening. Any serious acute bacterial infection, unless treated and completely resolved with antibiotics at least 2 weeks prior to the Week -6 Visit. Severe chronic or recurrent bacterial infections, such as recurrent pneumonia or chronic bronchiectasis. Current or chronic treatment with systemic immunosuppressive agents such as MTX, azathioprine, or mycophenolate mofetil; prednisone ≥10 mg/day or equivalent dose of other corticosteroid on a chronic basis (3 months or longer) would also meet exclusion criteria. History of any transplant surgery requiring maintenance immunosuppressive therapy. Known history of hepatitis B virus surface antigen positivity or hepatitis B DNA positivity. Known history of hepatitis C virus ribonucleic acid (RNA) positivity. Known history of Human Immunodeficiency Virus (HIV) positivity. Glucose-6-phosphate dehydrogenase deficiency (tested at the Screening Visit). Chronic renal impairment defined as estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73 m^2 or currently on dialysis. Non-compensated congestive heart failure or hospitalization for congestive heart failure within 3 months of the Screening Visit, uncontrolled arrhythmia, treatment for acute coronary syndrome (myocardial infarction or unstable angina), or uncontrolled blood pressure (>160/100 mmHg) prior to Randomization at Week -4. Pregnant, planning to become pregnant, breastfeeding, planning to impregnate female partner, or not on an effective form of birth control, as determined by the Investigator. Prior treatment with pegloticase, another recombinant uricase (rasburicase), or concomitant therapy with a polyethylene glycol-conjugated drug. Known allergy to pegylated products or history of anaphylactic reaction to a recombinant protein or porcine product. Contraindication to MTX treatment or MTX treatment considered inappropriate. Known intolerance to MTX. Receipt of an investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to MTX administration at Week -6 or plans to take an investigational drug during the study. Liver transaminase levels (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) > upper limit of normal (ULN) or albumin < the lower limit of normal (LLN) at the Screening Visit). Chronic liver disease. White blood cell count < 4,000/µL, hematocrit < 32 percent, or platelet count < 75,000/µL. Currently receiving systemic or radiologic treatment for ongoing cancer. History of malignancy within 5 years other than non-melanoma skin cancer or in situ carcinoma of cervix. Diagnosis of osteomyelitis. Known history of hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome. Unsuitable candidate for the study, based on the opinion of the Investigator (e.g., cognitive impairment), such that participation might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements or complete the study. Alcohol use in excess of 3 alcoholic beverages per week. A known intolerance to all protocol standard gout flare prophylaxis regimens (i.e. subject must be able to tolerate at least one: colchicine and/or non-steroidal anti inflammatory drugs and/or low dose prednisone ≤10 mg/day). Current pulmonary fibrosis, bronchiectasis or interstitial pneumonitis. If deemed necessary by the Investigator, a chest X-ray may be performed during Screening.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Horizon Therapeutics USA, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Orthopedic Physicians Alaska
City
Anchorage
State/Province
Alaska
ZIP/Postal Code
99508
Country
United States
Facility Name
Arizona Arthritis and Rheumatology Research, PLLC - Flagstaff
City
Flagstaff
State/Province
Arizona
ZIP/Postal Code
86001
Country
United States
Facility Name
Arizona Arthritis and Rheumatology Research, PLLC-West
City
Glendale
State/Province
Arizona
ZIP/Postal Code
85306
Country
United States
Facility Name
Arizona Arthritis and Rheumatology Research, PLLC-East
City
Mesa
State/Province
Arizona
ZIP/Postal Code
85210
Country
United States
Facility Name
Applied Research Center of Arkansas, Inc
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72212
Country
United States
Facility Name
TriWest Research Associates
City
El Cajon
State/Province
California
ZIP/Postal Code
92020
Country
United States
Facility Name
Advanced Investigative Medicine, Inc.
City
Hawthorne
State/Province
California
ZIP/Postal Code
90250
Country
United States
Facility Name
Axis Clinical Trials
City
Los Angeles
State/Province
California
ZIP/Postal Code
90036
Country
United States
Facility Name
ACRC Studies
City
Poway
State/Province
California
ZIP/Postal Code
92064
Country
United States
Facility Name
ClinEdge Sierra Rheumatology, Inc.
City
Roseville
State/Province
California
ZIP/Postal Code
95661
Country
United States
Facility Name
East Bay Rheumatology Medical Group, Inc.
City
San Leandro
State/Province
California
ZIP/Postal Code
94578
Country
United States
Facility Name
Providence St. John's Health Clinic
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Medvin Clinical Research
City
Tujunga
State/Province
California
ZIP/Postal Code
91042
Country
United States
Facility Name
San Fernando Valley Health Institute
City
Van Nuys
State/Province
California
ZIP/Postal Code
91405
Country
United States
Facility Name
Ventura Clinical Trials
City
Ventura
State/Province
California
ZIP/Postal Code
93003
Country
United States
Facility Name
University of Colorado Division of Rheumatology
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Denver Arthritis Clinic
City
Denver
State/Province
Colorado
ZIP/Postal Code
80230
Country
United States
Facility Name
Avail Clinical Research
City
DeLand
State/Province
Florida
ZIP/Postal Code
32720
Country
United States
Facility Name
Prohealth Research Center
City
Doral
State/Province
Florida
ZIP/Postal Code
33166
Country
United States
Facility Name
Omega Research Maitland
City
Orlando
State/Province
Florida
ZIP/Postal Code
32808
Country
United States
Facility Name
DMI Research
City
Pinellas Park
State/Province
Florida
ZIP/Postal Code
33782
Country
United States
Facility Name
Napa Research Center
City
Pompano Beach
State/Province
Florida
ZIP/Postal Code
33064
Country
United States
Facility Name
GCP Clinical Research
City
Tampa
State/Province
Florida
ZIP/Postal Code
33609
Country
United States
Facility Name
Florida Medical Clinic, LLC
City
Zephyrhills
State/Province
Florida
ZIP/Postal Code
33542
Country
United States
Facility Name
St. Luke's Clinic - Rheumatology
City
Meridian
State/Province
Idaho
ZIP/Postal Code
83642
Country
United States
Facility Name
MD Medical Research
City
Oxon Hill
State/Province
Maryland
ZIP/Postal Code
20745
Country
United States
Facility Name
The Center for Rheumatology and Bone Research
City
Wheaton
State/Province
Maryland
ZIP/Postal Code
20902
Country
United States
Facility Name
Infusion Associates
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49525
Country
United States
Facility Name
Clinical Research Institute of Michigan, LLC
City
Saint Clair Shores
State/Province
Michigan
ZIP/Postal Code
48081
Country
United States
Facility Name
Benefis Hospital
City
Great Falls
State/Province
Montana
ZIP/Postal Code
59405
Country
United States
Facility Name
Physician Research Collaboration, LLC
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68516
Country
United States
Facility Name
Santa Fe Rheumatology
City
Santa Fe
State/Province
New Mexico
ZIP/Postal Code
87505
Country
United States
Facility Name
Long Island Arthritis & Osteoporosis Care
City
Babylon
State/Province
New York
ZIP/Postal Code
11702
Country
United States
Facility Name
Buffalo Rheumatology and Medicine
City
Orchard Park
State/Province
New York
ZIP/Postal Code
14127
Country
United States
Facility Name
NorthEast Rheumatology/Atrium Health
City
Concord
State/Province
North Carolina
ZIP/Postal Code
28025
Country
United States
Facility Name
NorthEast Rheumatology
City
Concord
State/Province
North Carolina
ZIP/Postal Code
28025
Country
United States
Facility Name
Medication Management, LLC
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27408
Country
United States
Facility Name
ClinEdge PMG Research of Hickory, LLC
City
Hickory
State/Province
North Carolina
ZIP/Postal Code
28602
Country
United States
Facility Name
ClinEdge PMG Research of Salisbury, LLC
City
Salisbury
State/Province
North Carolina
ZIP/Postal Code
28144
Country
United States
Facility Name
Shelby Clinical Research, LLC
City
Shelby
State/Province
North Carolina
ZIP/Postal Code
28150
Country
United States
Facility Name
PMG Research of Wilmington, LLC
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28401
Country
United States
Facility Name
Premier Clinical/STAT Research
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45417
Country
United States
Facility Name
Paramount Medical Research & Consulting, LLC
City
Middleburg Heights
State/Province
Ohio
ZIP/Postal Code
44130
Country
United States
Facility Name
Clinical Research Source Inc.
City
Perrysburg
State/Province
Ohio
ZIP/Postal Code
43551
Country
United States
Facility Name
Premier Clinical/STAT Research - Springboro
City
Springboro
State/Province
Ohio
ZIP/Postal Code
45066
Country
United States
Facility Name
Altoona Center for Clinical Research
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Facility Name
Piedmont Arthritis Clinic
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29601
Country
United States
Facility Name
Articularis Healthcare Group
City
Summerville
State/Province
South Carolina
ZIP/Postal Code
29486
Country
United States
Facility Name
West Tennessee Research Institute
City
Jackson
State/Province
Tennessee
ZIP/Postal Code
38305
Country
United States
Facility Name
Ramesh C. Gupta, M.D.
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38119
Country
United States
Facility Name
Diagnostic and Interventional Nephrology Of Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77004
Country
United States
Facility Name
Research Consultants - Frostwood
City
Houston
State/Province
Texas
ZIP/Postal Code
77024
Country
United States
Facility Name
Research Consultants - Astoria
City
Houston
State/Province
Texas
ZIP/Postal Code
77089
Country
United States
Facility Name
Arthritis Clinic of Central Texas
City
San Marcos
State/Province
Texas
ZIP/Postal Code
78666
Country
United States
Facility Name
Arthritis & Osteoporosis Clinic - Waco
City
Waco
State/Province
Texas
ZIP/Postal Code
76710
Country
United States
Facility Name
Clear Lake Specialties
City
Webster
State/Province
Texas
ZIP/Postal Code
77598
Country
United States
Facility Name
Western Washington Arthritis Clinic
City
Bothell
State/Province
Washington
ZIP/Postal Code
98021
Country
United States
Facility Name
Arthritis Northwest
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
Rheumatic Disease Center
City
Glendale
State/Province
Wisconsin
ZIP/Postal Code
53219
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

Study of KRYSTEXXA® (Pegloticase) Plus Methotrexate in Participants With Uncontrolled Gout

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