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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 )

Tracking Information
First Submitted Date  ICMJE August 11, 2020
First Posted Date  ICMJE August 13, 2020
Last Update Posted Date December 22, 2020
Actual Study Start Date  ICMJE October 2, 2020
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 11, 2020)
The incidence of participants experiencing Infusion Reactions (IRs), including anaphylaxis related to pegloticase [ Time Frame: Day 1 through Week 24. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 11, 2020)
  • 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.
  • 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.
  • 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 ]
  • Time to first infusion reaction leading to slowing down of the infusion rate or discontinuation of treatment [ Time Frame: Day 1 to Week 24 ]
  • Time to first infusion reaction [ Time Frame: Day 1 to Week 24 ]
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Infusion Duration Study To Assess Tolerability of Pegloticase Administered With a Shorter Infusion Duration in Subjects With Uncontrolled Gout Receiving Methotrexate
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE 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
Condition  ICMJE
  • Chronic Uncontrolled Gout
  • Gout
  • Uncontrolled Gout
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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
    Intervention: Biological: Pegloticase with MTX
  • 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
    Intervention: Biological: Pegloticase with MTX
  • 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
    Intervention: Biological: Pegloticase with MTX
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 11, 2020)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: HorizonTherapeutics 1-866-479-6742 clinicaltrials@horizontherapeutics.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04511702
Other Study ID Numbers  ICMJE HZNP-KRY-403
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Horizon Pharma Ireland, Ltd., Dublin Ireland ( Horizon Therapeutics Ireland DAC )
Study Sponsor  ICMJE Horizon Therapeutics Ireland DAC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Supra Verma, MD Horizon Therapeutics Ireland DAC
PRS Account Horizon Pharma Ireland, Ltd., Dublin Ireland
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP