Study of KRYSTEXXA® (Pegloticase) Plus Methotrexate in Participants With Uncontrolled Gout
MIRROR RCT
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])
1 other identifier
interventional
152
1 country
60
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_4
Started Jun 2019
Typical duration for phase_4
60 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 13, 2019
CompletedFirst Submitted
Initial submission to the registry
June 19, 2019
CompletedFirst Posted
Study publicly available on registry
June 21, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 17, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
April 11, 2022
CompletedResults Posted
Study results publicly available
May 16, 2022
CompletedJune 26, 2024
June 1, 2024
1.8 years
June 19, 2019
March 4, 2022
June 14, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
Month 6 (Weeks 20, 21, 22, 23 and 24)
Secondary Outcomes (5)
Percentage of sUA (sUA < 6 mg/dL) Responders During Month 12
Month 12 (Weeks 48, 50 and 52)
Percentage of Participants With Complete Resolution of ≥ 1 Tophi at Week 52
Baseline, Week 52
Mean Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52
Baseline, Week 52
Mean Change From Baseline HAQ Pain Score at Week 52
Baseline, Week 52
Mean Change From Baseline in HAQ Health Score at Week 52
Baseline, Week 52
Study Arms (2)
Pegloticase + MTX
EXPERIMENTALFollowing 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.
Pegloticase + Placebo
PLACEBO COMPARATORFollowing 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.
Interventions
IV pegloticase 8 mg Q2W
Folic acid 1 mg orally every day beginning at Week -6 until prior to the Week 52 Visit.
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.
For IR prophylaxis, fexofenadine (180 mg orally) taken the day before each infusion and on the morning of each infusion.
For IR prophylaxis, acetaminophen (1000 mg orally) taken the morning of each infusion.
For IR prophylaxis, methylprednisolone (125 mg IV) given over an infusion duration between 10 - 30 minutes, immediately prior to each infusion.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- 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.
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Amgenlead
Study Sites (60)
University of Alabama
Birmingham, Alabama, 35294, United States
Orthopedic Physicians Alaska
Anchorage, Alaska, 99508, United States
Arizona Arthritis and Rheumatology Research, PLLC - Flagstaff
Flagstaff, Arizona, 86001, United States
Arizona Arthritis and Rheumatology Research, PLLC-West
Glendale, Arizona, 85306, United States
Arizona Arthritis and Rheumatology Research, PLLC-East
Mesa, Arizona, 85210, United States
Applied Research Center of Arkansas, Inc
Little Rock, Arkansas, 72212, United States
TriWest Research Associates
El Cajon, California, 92020, United States
Advanced Investigative Medicine, Inc.
Hawthorne, California, 90250, United States
Axis Clinical Trials
Los Angeles, California, 90036, United States
ACRC Studies
Poway, California, 92064, United States
ClinEdge Sierra Rheumatology, Inc.
Roseville, California, 95661, United States
East Bay Rheumatology Medical Group, Inc.
San Leandro, California, 94578, United States
Providence St. John's Health Clinic
Santa Monica, California, 90404, United States
Medvin Clinical Research
Tujunga, California, 91042, United States
San Fernando Valley Health Institute
Van Nuys, California, 91405, United States
Ventura Clinical Trials
Ventura, California, 93003, United States
University of Colorado Division of Rheumatology
Aurora, Colorado, 80045, United States
Denver Arthritis Clinic
Denver, Colorado, 80230, United States
Avail Clinical Research
DeLand, Florida, 32720, United States
Prohealth Research Center
Doral, Florida, 33166, United States
Omega Research Maitland
Orlando, Florida, 32808, United States
DMI Research
Pinellas Park, Florida, 33782, United States
Napa Research Center
Pompano Beach, Florida, 33064, United States
GCP Clinical Research
Tampa, Florida, 33609, United States
Florida Medical Clinic, LLC
Zephyrhills, Florida, 33542, United States
St. Luke's Clinic - Rheumatology
Meridian, Idaho, 83642, United States
MD Medical Research
Oxon Hill, Maryland, 20745, United States
The Center for Rheumatology and Bone Research
Wheaton, Maryland, 20902, United States
Infusion Associates
Grand Rapids, Michigan, 49525, United States
Clinical Research Institute of Michigan, LLC
Saint Clair Shores, Michigan, 48081, United States
Benefis Hospital
Great Falls, Montana, 59405, United States
Physician Research Collaboration, LLC
Lincoln, Nebraska, 68516, United States
Santa Fe Rheumatology
Santa Fe, New Mexico, 87505, United States
Long Island Arthritis & Osteoporosis Care
Babylon, New York, 11702, United States
Buffalo Rheumatology and Medicine
Orchard Park, New York, 14127, United States
NorthEast Rheumatology/Atrium Health
Concord, North Carolina, 28025, United States
NorthEast Rheumatology
Concord, North Carolina, 28025, United States
Medication Management, LLC
Greensboro, North Carolina, 27408, United States
ClinEdge PMG Research of Hickory, LLC
Hickory, North Carolina, 28602, United States
ClinEdge PMG Research of Salisbury, LLC
Salisbury, North Carolina, 28144, United States
Shelby Clinical Research, LLC
Shelby, North Carolina, 28150, United States
PMG Research of Wilmington, LLC
Wilmington, North Carolina, 28401, United States
Premier Clinical/STAT Research
Dayton, Ohio, 45417, United States
Paramount Medical Research & Consulting, LLC
Middleburg Heights, Ohio, 44130, United States
Clinical Research Source Inc.
Perrysburg, Ohio, 43551, United States
Premier Clinical/STAT Research - Springboro
Springboro, Ohio, 45066, United States
Altoona Center for Clinical Research
Duncansville, Pennsylvania, 16635, United States
Piedmont Arthritis Clinic
Greenville, South Carolina, 29601, United States
Articularis Healthcare Group
Summerville, South Carolina, 29486, United States
West Tennessee Research Institute
Jackson, Tennessee, 38305, United States
Ramesh C. Gupta, M.D.
Memphis, Tennessee, 38119, United States
Diagnostic and Interventional Nephrology Of Houston
Houston, Texas, 77004, United States
Research Consultants - Frostwood
Houston, Texas, 77024, United States
Research Consultants - Astoria
Houston, Texas, 77089, United States
Arthritis Clinic of Central Texas
San Marcos, Texas, 78666, United States
Arthritis & Osteoporosis Clinic - Waco
Waco, Texas, 76710, United States
Clear Lake Specialties
Webster, Texas, 77598, United States
Western Washington Arthritis Clinic
Bothell, Washington, 98021, United States
Arthritis Northwest
Spokane, Washington, 99204, United States
Rheumatic Disease Center
Glendale, Wisconsin, 53219, United States
Related Publications (3)
Botson J, Obermeyer K, LaMoreaux B, Padnick-Silver L, Verma S, Weinblatt ME, Peterson J. Quality of life and clinical gout assessments during pegloticase with and without methotrexate co-therapy: MIRROR randomized controlled trial exploratory findings. Rheumatol Adv Pract. 2024 Nov 29;8(4):rkae145. doi: 10.1093/rap/rkae145. eCollection 2024.
PMID: 39678124DERIVEDDalbeth N, Botson J, Saag K, Kumar A, Padnick-Silver L, LaMoreaux B, Becce F. Monosodium urate crystal depletion and bone erosion remodeling during pegloticase treatment in patients with uncontrolled gout: Exploratory dual-energy computed tomography findings from MIRROR RCT. Joint Bone Spine. 2024 Jul;91(4):105715. doi: 10.1016/j.jbspin.2024.105715. Epub 2024 Mar 4.
PMID: 38447697DERIVEDBotson JK, Saag K, Peterson J, Parikh N, Ong S, La D, LoCicero K, Obermeyer K, Xin Y, Chamberlain J, LaMoreaux B, Verma S, Sainati S, Grewal S, Majjhoo A, Tesser JRP, Weinblatt ME. A Randomized, Placebo-Controlled Study of Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving Pegloticase: Primary Efficacy and Safety Findings. Arthritis Rheumatol. 2023 Feb;75(2):293-304. doi: 10.1002/art.42335. Epub 2022 Dec 16.
PMID: 36099211DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Monitor
- Organization
- Horizon Therapeutics USA, Inc.
Study Officials
- STUDY DIRECTOR
MD
Amgen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 19, 2019
First Posted
June 21, 2019
Study Start
June 13, 2019
Primary Completion
March 17, 2021
Study Completion
April 11, 2022
Last Updated
June 26, 2024
Results First Posted
May 16, 2022
Record last verified: 2024-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
- Access Criteria
- Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.