Observational Study of the Use of Pegloticase (KRYSTEXXA®) in Refractory Chronic Gout (EyesOnGOUT)

Observational Study of the Use of KRYSTEXXA® (Pegloticase) in Adult Hyperuricemic Patients With Gout Refractory to Conventional Therapy

The primary purpose of this study is to observe patients being treated with pegloticase in a standard healthcare setting in order to evaluate the frequency and severity of infusion reactions, anaphylaxis and immune complex related events. Additionally, serious adverse events associated with pegloticase therapy will be identified.

Study Overview

• Status: Completed
• Conditions: Refractory Chronic Gout
• Intervention / Treatment: Biological: Pegloticase

Detailed Description

This was a Phase 4, multicenter, open-label, single-arm observational study of pegloticase 8 mg administered intravenously every 2 weeks in adult hyperuricemic patients with gout refractory to conventional therapy. Study duration is approximately 63 weeks, including 51 weeks of treatment and 12 weeks of follow-up.

The design of this study follows the FDA-approved Full Prescribing Information for the use of pegloticase and allows for capturing additional data related to the safety and efficacy of pegloticase within the standard healthcare setting.

• Study Type: Observational
• Enrollment (Actual): 188

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Rheumatology Associates, Pc
    • Birmingham, Alabama, United States, 35294
      • UAB Rheumatology
    • Huntsville, Alabama, United States, 35801
      • Saadat Ansari, MD, LLC
  • California
    • Covina, California, United States, 91723
      • Medvin Clinical Research
    • Laguna Hills, California, United States, 92653
      • Alliance Clinical Research, LLC
    • Lakewood, California, United States, 90712
      • Advanced Medical Research, LLC
    • Los Angeles, California, United States, 90045
      • Pacific Arthritis Care Center
    • Monterey Park, California, United States, 91754
      • R Srinivasan, MD, Inc
    • Murrieta, California, United States, 92563
      • Brigid Freyne, MD, Inc
    • Poway, California, United States, 92064
      • Alliance Clinical Research
  • Colorado
    • Denver, Colorado, United States, 80218
      • Denver Nephrologists, PC
  • Connecticut
    • Trumbull, Connecticut, United States, 06611
      • New England Research Associates, LLC
  • District of Columbia
    • Washington, District of Columbia, United States, 20060
      • Howard University Hospital
    • Washington, District of Columbia, United States, 20422
      • Washington DC Veteran's Affairs Medical Center
  • Florida
    • Brandon, Florida, United States, 33511
      • Bay Area Arthritis and Osteoporosis
    • Clearwater, Florida, United States, 33761
      • Countryside Arthritis Center
    • Jupiter, Florida, United States, 33458
      • Science and Research Institute, Inc
    • Miami, Florida, United States, 33174
      • A & O Research Center
    • Palm Harbor, Florida, United States, 34684
      • Arthritis Research Of Florida, Inc.
    • Pembroke Pines, Florida, United States, 33026
      • Family Clinical Trials, LLC
    • Tampa, Florida, United States, 33604
      • Jedidiah Clinical Research
    • Tampa, Florida, United States, 33614
      • Midtown Medical Center
  • Georgia
    • Calhoun, Georgia, United States, 30701
      • Global Research Partners & Consultants, Inc.
    • Stockbridge, Georgia, United States, 30281
      • Arthritis Research & Treatment Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46227
      • Diagnostic Rheumatology and Research PC
  • Iowa
    • Cedar Rapids, Iowa, United States, 52401
      • Physicians' Clinic of Iowa, P.C.
  • Kentucky
    • Mount Sterling, Kentucky, United States, 40353
      • Central Kentucky Research Associates of Kentucky
    • Owensboro, Kentucky, United States, 42303
      • Research Integrity, LLC
  • Louisiana
    • Eunice, Louisiana, United States, 70535
      • Horizon Research Group of Opelousas, LLC
    • Monroe, Louisiana, United States, 71203
      • Arthritis and Diabetes Clinic, Inc.
  • Maryland
    • Bethesda, Maryland, United States, 20889-5630
      • Walter Reed National Military Medical Center
    • Hagerstown, Maryland, United States, 21740
      • Klein & Associates MD, PA.
    • Wheaton, Maryland, United States, 20902
      • The Center for Rheumatology and Bone Research
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Clinical Pharmacology Study Groups
    • Worcester, Massachusetts, United States, 01605
      • Reliant Medical Group, Inc.
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5422
      • University of Michigan Health System
    • Caro, Michigan, United States, 48723
      • Caro Health Plaza
    • Grand Rapids, Michigan, United States, 49525
      • Infusion Associates
    • Lansing, Michigan, United States, 48910
      • Justus J. Fiechtner, MD, PC
    • Saint Clair Shores, Michigan, United States, 48081
      • Shores Rheumatology, PC
  • Minnesota
    • Eagan, Minnesota, United States, 55121
      • Saint Paul Rheumatology, PA
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Kansas City Internal Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89118
      • Arthritis Medical Clinic
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Rheumatology Associates of North Jersey
  • New York
    • Smithtown, New York, United States, 11787
      • Rheumatology Associates of Long Island
  • North Carolina
    • Concord, North Carolina, United States, 28025
      • NorthEast Rheumatology
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27832
      • Physicians East, PA
    • Raleigh, North Carolina, United States, 27617
      • Shanahan Rheumatology and Immunotherapy, PLLC
    • Sanford, North Carolina, United States, 27330
      • Specialty Medical Clinic and Research Center
  • Ohio
    • Portsmouth, Ohio, United States, 45662
      • Southern Ohio Rheumatology
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • Keystone Pain Institute, Ilumina Clinical Associates
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Low Country Rheumatology
    • Orangeburg, South Carolina, United States, 29118
      • Acme Research L.L.C.
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Ramesh C. Gupta, M.D.
  • Texas
    • Austin, Texas, United States, 78731
      • Austin Regional Clinic
    • El Paso, Texas, United States, 79902
      • Dr. Raj Marwah
    • Houston, Texas, United States, 77004
      • Rheumatic Disease Clinical Research Center
    • Houston, Texas, United States, 77004
      • Diagnostic Clinic of Houston
  • Virginia
    • Arlington, Virginia, United States, 22205
      • Arthritis Clinic Of Northern Virginia, P.C.
    • Manassas, Virginia, United States, 20109
      • Arthritis & Osteoporosis Center of North Virginia
    • Norfolk, Virginia, United States, 23502
      • Sentara Rheumatology Specialists
  • Washington
    • Kennewick, Washington, United States, 99336
      • Apex Clinical Research
  • West Virginia
    • Clarksburg, West Virginia, United States, 26301
      • Mountain State Clinical Research
  • Wisconsin
    • Glendale, Wisconsin, United States, 53217
      • Rheumatic Disease Center, LLP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The patient population in this study will be hyperuricemic (serum uric acid (SUA) > 6 mg/dL) adult men and women (age 18 or greater) diagnosed with chronic gout and who are refractory to conventional therapy. Gout refractory to conventional therapy occurs in patients who have failed to normalize SUA and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom these drugs are contraindicated. To enter this study, the patient and the physician must have decided to begin treatment with KRYSTEXXA.

Description

Inclusion Criteria:

• Adults (age 18 years or more) with chronic gout refractory to conventional therapy, defined as patients who have failed to normalize SUA and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose, or for whom these drugs are contraindicated.
• Patients who have made the decision, along with their treating physician, to begin treatment with KRYSTEXXA.
• Patients who are willing and able to give informed consent and adhere to visit/protocol schedules.

Exclusion Criteria:

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Non-compensated congestive heart failure
• Pregnancy or breast feeding
• Prior treatment with pegloticase or another recombinant uricase
• Known allergy to urate oxidase
• Prior treatment or concomitant therapy with a polyethylene glycol (PEG)-conjugated drug
• Recipient of an investigational drug within 4 weeks prior to study drug administration or plans to take an investigational agent during the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pegloticase; Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.	Biological: Pegloticase; Pegloticase 8 mg intravenous every 2 weeks; Other Names: KRYSTEXXA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Infusion Reactions	Infusion reactions were defined as adverse events (AEs) or clusters of events, not attributable to another cause that occurred during or within 2 hours after the infusion of pegloticase. Any other case that occurred outside of the 2-hour window was categorized per Investigator discretion.	52 weeks
Number of Participants With Anaphylaxis	Anaphylaxis was defined using the National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria: Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., generalized hives; pruritus or flushing; swollen lips, tongue, or uvula), and at least 1 of the following: Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow, hypoxemia).; Reduced blood pressure (i.e., systolic blood pressure < 90 mm Hg or greater than 30% decrease from that patient's baseline) or associated symptoms of end-organ failure (e.g., hypotonia [collapse], syncope, incontinence).	52 weeks
Number of Participants With Immune Complex-related Events	Immune complex-related events were defined as any presumptive immune complex-related disorders that were confirmed by an appropriate investigation of the event and of complement markers (C3 and C4 levels). Clinical manifestations could have included skin rash, arthralgia, arthritis, proteinuria, serum sickness, and cryoglobulinemia.	From first dose of study drug to the end of the 12-week follow-up period (63 weeks).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Normalization of Serum Uric Acid at Week 24 and Week 52	Normalization of serum uric acid was defined as serum uric acid value less than 6 mg/dL.	Week 24 and week 52
Change From Baseline in Number of Gout Flares	The number of gout flares occurring in the 2 weeks prior to each visit. Baseline number of flares was calculated as the average number of flares that occurred in the 6-month baseline period divided by 12 weeks.	Baseline, week 24 and week 48
Number of Swollen Joints Over Time		Baseline and weeks 24 and 52
Number of Tender Joints Over Time		Baseline and weeks 24 and 52
Number of Palpable Tophi Over Time	Gout tophi are nodular deposits of urate crystals and inflammatory cells in joints, soft tissues, bones, and in some organs.	Baseline and weeks 24 and 52

Collaborators and Investigators

• Sponsor: Horizon Pharma Rheumatology LLC
• Investigators: Study Director: Jeffery Nieves, PharmD, Horizon Pharma Rheumatology LLC

Publications and helpful links

General Publications

• Sundy JS, Baraf HS, Yood RA, Edwards NL, Gutierrez-Urena SR, Treadwell EL, Vazquez-Mellado J, White WB, Lipsky PE, Horowitz Z, Huang W, Maroli AN, Waltrip RW 2nd, Hamburger SA, Becker MA. Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. JAMA. 2011 Aug 17;306(7):711-20. doi: 10.1001/jama.2011.1169.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2011
• Primary Completion (Actual): June 30, 2017
• Study Completion (Actual): June 30, 2017

Study Registration Dates

• First Submitted: October 28, 2011
• First Submitted That Met QC Criteria: November 4, 2011
• First Posted (Estimate): November 6, 2011

Study Record Updates

• Last Update Posted (Actual): January 11, 2019
• Last Update Submitted That Met QC Criteria: June 29, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Metabolism, Inborn Errors; Crystal Arthropathies; Purine-Pyrimidine Metabolism, Inborn Errors; Gout
• Other Study ID Numbers: M0401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided