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Infusion Duration Study To Assess Tolerability of Pegloticase Administered With a Shorter Infusion Duration in Subjects With Uncontrolled Gout Receiving Methotrexate

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ClinicalTrials.gov Identifier: NCT04511702
Recruitment Status : Recruiting
First Posted : August 13, 2020
Last Update Posted : December 22, 2020
Sponsor:
Information provided by (Responsible Party):
Horizon Pharma Ireland, Ltd., Dublin Ireland ( Horizon Therapeutics Ireland DAC )

Study Description
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Brief Summary:
The purpose of this study is to assess the tolerability of pegloticase administered with a shorter infusion duration in participants with uncontrolled gout receiving methotrexate.

Condition or disease Intervention/treatment Phase
Chronic Uncontrolled Gout Gout Uncontrolled Gout Biological: Pegloticase with MTX Phase 4

Detailed Description:
Approximately 30-50 participants will be enrolled. After a 4-week methotrexate run-in period, participants will be treated for up to 24 weeks with weekly oral methotrexate and biweekly 8mg pegloticase infusions. Up to three pegloticase infusion durations will be assessed in the study: 60-minute infusion, 45-minute infusion and 30-minute infusion. Safety evaluations will be performed regularly throughout the course of the study.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Three different infusion durations may be used. 60-minute infusion, 45-minute infusion and 30-minute and each will include 10 participants.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 4, Multicenter, Open-Label, Infusion Duration Study To Assess Tolerability of Pegloticase Administered With a Shorter Infusion Duration in Subjects With Uncontrolled Gout Receiving Methotrexate
Actual Study Start Date : October 2, 2020
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Gout
MedlinePlus related topics: Gout

Arms and Interventions
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Arm Intervention/treatment
Experimental: Pegloticase 60 Minute Infusion with methotrexate (MTX)
Pegloticase 60 Minute Infusion with methotrexate (MTX). Participants will receive MTX (15 mg) (weekly) during the Run-in Period, then pegloticase (every 2 weeks) with MTX (weekly) for 24 weeks
 Biological: Pegloticase with MTX
Participants will receive MTX during the run-in period then pegloticase with MTX for up to 24 weeks during the treatment period
Other Name: Methotrexate
Experimental: Pegloticase 45 Minute Infusion with methotrexate (MTX)
Pegloticase 45 Minute Infusion with methotrexate (MTX). Participants will receive MTX (15 mg) (weekly) during the Run-in Period, then pegloticase (every 2 weeks) with MTX (weekly) for 24 weeks
 Biological: Pegloticase with MTX
Participants will receive MTX during the run-in period then pegloticase with MTX for up to 24 weeks during the treatment period
Other Name: Methotrexate
Experimental: Pegloticase 30 Minute Infusion with methotrexate (MTX)
Pegloticase 30 Minute Infusion with methotrexate (MTX). Participants will receive MTX (15 mg) (weekly) during the Run-in Period, then pegloticase (every 2 weeks) with MTX (weekly) for 24 weeks
 Biological: Pegloticase with MTX
Participants will receive MTX during the run-in period then pegloticase with MTX for up to 24 weeks during the treatment period
Other Name: Methotrexate


Outcome Measures
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Primary Outcome Measures :
  1. The incidence of participants experiencing Infusion Reactions (IRs), including anaphylaxis related to pegloticase [ Time Frame: Day 1 through Week 24. ]

Secondary Outcome Measures :
  1. Proportion of participants who experienced any of the following events: infusion reaction leading to discontinuation of treatment, anaphylaxis, or meeting Individual participant sUA Discontinuation Criteria [ Time Frame: Day 1 to Week 24 ]
    A participant meets the Individual participant sUA Discontinuation Criteria if he or she has a pre-infusion sUA level >6 mg/dL at 2 consecutive study visits beginning with the Week 2 Visit. When this occurs, the participants must discontinue treatment, with the option to continue on the study.

  2. Time to any of the following events: infusion reaction leading to discontinuation of treatment, anaphylaxis, or meeting Individual participant sUA Discontinuation Criteria [ Time Frame: Day 1 to Week 24 ]
    A participant meets the Individual participant sUA Discontinuation Criteria if he or she has a pre-infusion sUA level >6 mg/dL at 2 consecutive study visits beginning with the Week 2 Visit. When this occurs, the participants must discontinue treatment, with the option to continue on the study.

  3. Proportion of participants who experienced infusion reaction leading to slowing down of the infusion rate or discontinuation of treatment [ Time Frame: Day 1 to Week 24 ]
  4. Time to first infusion reaction leading to slowing down of the infusion rate or discontinuation of treatment [ Time Frame: Day 1 to Week 24 ]
  5. Time to first infusion reaction [ Time Frame: Day 1 to Week 24 ]
  6. Proportion of participants who were able to complete all infusions over the assigned treatment duration length or a lesser time, without clinically requiring an increased infusion time [ Time Frame: Day 1 to Week 24 ]
  7. Proportion of infusions completed over the assigned duration length or a lesser time, without clinically requiring an increased infusion time [ Time Frame: Day 1 to Week 24 ]

Eligibility Criteria
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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:

  1. Adult men or women ≥18 years of age.

  2. Uncontrolled gout, defined as meeting the following criteria:

    • Hyperuricemia during the screening period defined as sUA ≥6 mg/dL
    • Failure to maintain normalization of sUA with xanthine oxidase inhibitors at the maximum medically appropriate dose, or with intolerable side effects or a contraindication to xanthine oxidase inhibitor therapy based on medical record review or subject interview

    • 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
  3. Willing to discontinue all oral urate-lowering therapy at least 7 days prior to MTX dosing at Week -4 and remain off of urate lowering therapy when receiving pegloticase infusions during the study.
  4. Able to tolerate MTX 15 mg for 4 weeks during the MTX Run-in Period prior to the first dose of pegloticase.

Exclusion Criteria:

  1. 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 (defined as 3 months or longer) would also meet exclusion criteria.
  2. Known history of any solid organ transplant surgery requiring maintenance Immunosuppressive therapy unless treated and no chronic or active infection confirmed by HBV serology.
  3. Known history of hepatitis B virus surface antigen positivity or hepatitis B DNA positivity, unless treated and viral load is negative and no chronic or active infection confirmed by HBV serology.
  4. Known history of Human Immunodeficiency Virus (HIV) positivity.
  5. Glucose-6-phosphate dehydrogenase (G6PD) deficiency (tested at Screening Visit).
  6. Severe chronic renal impairment (estimated glomerular filtration rate <40 mL/min/1.73 m2) at the Screening Visit based on 4 variable-Modification of Diet in Renal Disease [MDRD] formula or currently on dialysis.
  7. Non-compensated congestive heart failure or hospitalization for congestive heart failure or treatment for acute coronary syndrome (myocardial infarction or unstable angina) within 3 months of the Screening Visit, or current uncontrolled arrhythmia, or current uncontrolled blood pressure (BP) (>160/100 mmHg) prior to Week -4.
  8. 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.
  9. Prior treatment with pegloticase (KRYSTEXXA), another recombinant uricase (rasburicase), or concomitant therapy with a polyethylene glycol-conjugated drug.
  10. Known intolerance to MTX.
  11. Chronic liver disease.
  12. Currently receiving systemic or radiologic treatment for ongoing cancer.
  13. History of malignancy within 5 years other than non-melanoma skin cancer or in situ carcinoma of cervix.
  14. Known history of hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome.
  15. Current pulmonary fibrosis, bronchiectasis or interstitial pneumonitis. If deemed necessary by the Investigator, a chest X-ray may be performed during Screening.
Contacts and Locations
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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): NCT04511702


Contacts
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Contact: HorizonTherapeutics 1-866-479-6742 clinicaltrials@horizontherapeutics.com

Locations
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United States, Alaska
Orthopedic Physicians Alaska Recruiting
Anchorage, Alaska, United States, 99508
Contact: Anna Campione    907-341-5220    acampione@opaak.com   
Principal Investigator: John Botson, MD         
United States, California
Amicis Research Center Recruiting
Northridge, California, United States, 91324
Contact: Tyrone Rosales    818-924-4708    Tyrone.rosales@amicisresearch.com   
Principal Investigator: Pascal Dabel, MD         
Medvin Clinical Research Recruiting
Tujunga, California, United States, 91042
Contact: Melanie Robleto    213-281-5146    melanie@medvinresearch.com   
Principal Investigator: Dan La, MD         
United States, Colorado
Denver Arthritis Clinic Recruiting
Denver, Colorado, United States, 80230
Contact: Theresa Hernandez    303-394-2828 ext 177    thernandez@dacdenver.com   
Principal Investigator: Christopher Antolini, MD         
United States, Florida
Napa Research Center Recruiting
Boca Raton, Florida, United States, 33432
Contact: Magda Hernandez    305-960-7934    mhernandez@napatrials.com   
Principal Investigator: Naval Parikh, MD         
GCP Clinical Research Recruiting
Tampa, Florida, United States, 33064
Contact: Marlene Klingeman    321-315-0780    marlenek@gcpclinicalresearch.com   
Principal Investigator: Karon Locicero, MD         
United States, Maryland
MD Medical Research Recruiting
Oxon Hill, Maryland, United States, 20745
Contact: Marie Edwards    301-329-2608    marie.edwards@mdmedicalresearch.com   
Principal Investigator: Stephen Ong, MD         
United States, North Carolina
PMG Research of Hickory, LLC Recruiting
Hickory, North Carolina, United States, 28602
Contact: Nicole Everhart    828-345-5060    nicole.everhart@pmg-research.com   
Principal Investigator: Dennis Payne, MD         
PMG Research of Salisbury, LLC Recruiting
Salisbury, North Carolina, United States, 28144
Contact: Stacy Smith    704-647-9913    stacy.smith@pmg-research.com   
Principal Investigator: Rakesh Patel, DO         
Shelby Clinical Research, LLC Recruiting
Shelby, North Carolina, United States, 28150
Contact: Pamela Seagle    980-552-9230    pseagle@shelbyclinicalresearch.com   
Principal Investigator: Christopher Martin, MD         
United States, Pennsylvania
Altoona Center for Clinical Research Recruiting
Duncansville, Pennsylvania, United States, 16635
Contact: Pam Morrison    814-693-0300 ext 144    pammorrison@altoonaresearch.com   
Principal Investigator: Alan Kivitz, MD         
United States, Texas
Abigail Rebecca Neiman, MD, PA Recruiting
Houston, Texas, United States, 77024
Contact: Hassan Arshad    713-932-0054    Hassan@biopharmainfo.net   
Principal Investigator: Abigail R Neiman, MD         
United States, Washington
Arthritis Northwest Recruiting
Spokane, Washington, United States, 99204
Contact: Terri Cone    509-838-6500 ext 310    tcone@arthritisnw.com   
Principal Investigator: Jeffrey Butler, MD         
Sponsors and Collaborators
Horizon Therapeutics Ireland DAC
Investigators
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Study Director: Supra Verma, MD Horizon Therapeutics Ireland DAC
More Information
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Responsible Party: Horizon Therapeutics Ireland DAC
ClinicalTrials.gov Identifier: NCT04511702    
Other Study ID Numbers: HZNP-KRY-403
First Posted: August 13, 2020    Key Record Dates
Last Update Posted: December 22, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Horizon Pharma Ireland, Ltd., Dublin Ireland ( Horizon Therapeutics Ireland DAC ):
gout
uncontrolled gout
Additional relevant MeSH terms:
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Gout
Arthritis
Joint Diseases
Musculoskeletal Diseases
Crystal Arthropathies
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
 Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors