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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 6, 2022
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 safety, tolerability and efficiency 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 180 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 : 180 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 4, Multicenter, Open-Label, Infusion Duration Study To Assess Safety, Tolerability and Efficacy 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 : September 2024
Estimated Study Completion Date : December 2024

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. The proportion of Month 6 (Weeks 20, 22 and 24) responders, defined as subjects achieving and maintaining sUA<6mg/dL for at least 80% of the time during Month 6. [ 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. Time to any of the following events: IR leading to discontinuation of treatment, anaphylaxis, or meeting individual Subject sUA Discontinuation Criteria (two consecutive pre-infusion sUAs > 6mg/dL. [ 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.

Exclusion Criteria:

  1. Severe chronic or recurrent bacterial infections, such as recurrent pneumonia or chronic bronchiectasis.
  2. 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.
  3. Glucose-6-phosphate dehydrogenase (G6PD) deficiency (tested at Screening Visit).
  4. 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.
  5. 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.
  6. 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.
  7. Prior treatment with pegloticase (KRYSTEXXA), another recombinant uricase (rasburicase), or concomitant therapy with a polyethylene glycol-conjugated drug.
  8. Currently receiving systemic or radiologic treatment for ongoing cancer.
  9. History of malignancy within 5 years other than non-melanoma skin cancer or in situ carcinoma of cervix.
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: Horizon Therapeutics DAC 1-866-479-6742 clinicaltrials@horizontherapeutics.com

Locations
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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 6, 2022
Last Verified: December 2022
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