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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

Sponsor
Horizon Therapeutics Ireland DAC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04511702
Collaborator
(none)
80
Enrollment
13
Locations
3
Arms
35
Anticipated Duration (Months)
6.2
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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
  • Biological: Pegloticase with MTX
 Phase 4

Detailed Description

Approximately 80-100 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

Study Type:
Interventional
Anticipated Enrollment :
80 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.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 :
Oct 2, 2020
Anticipated Primary Completion Date :
Jul 1, 2023
Anticipated Study Completion Date :
Sep 1, 2023

Arms and Interventions

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 Names:
  • 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 Names:
  • 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 Names:
  • Methotrexate

    		•

    Outcome Measures

    Primary Outcome Measures

    1. The incidence of participants experiencing Infusion Reactions (IRs), including anaphylaxis related to pegloticase [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. [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. [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. [Day 1 to Week 24]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    1. 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

    Locations

    Site City State Country Postal Code
    1 Orthopedic Physicians Alaska Anchorage Alaska United States 99508
    2 Amicis Research Center Northridge California United States 91324
    3 Medvin Clinical Research Tujunga California United States 91042
    4 Denver Arthritis Clinic Denver Colorado United States 80230
    5 Napa Research Center Pompano Beach Florida United States 33064
    6 GCP Clinical Research Tampa Florida United States 33064
    7 MD Medical Research Oxon Hill Maryland United States 20745
    8 PMG Research of Hickory, LLC Hickory North Carolina United States 28602
    9 PMG Research of Salisbury, LLC Salisbury North Carolina United States 28144
    10 Shelby Clinical Research, LLC Shelby North Carolina United States 28150
    11 Altoona Center for Clinical Research Duncansville Pennsylvania United States 16635
    12 Abigail Rebecca Neiman, MD, PA Houston Texas United States 77024
    13 Arthritis Northwest Spokane Washington United States 99204

    Sponsors and Collaborators

    • Horizon Therapeutics Ireland DAC

    Investigators

    • Study Director: Supra Verma, MD, Horizon Therapeutics Ireland DAC

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Horizon Therapeutics Ireland DAC
    ClinicalTrials.gov Identifier:
    NCT04511702
    Other Study ID Numbers:
    • HZNP-KRY-403
    First Posted:
    Aug 13, 2020
    Last Update Posted:
    Apr 4, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Horizon Therapeutics Ireland DAC
    gout
    uncontrolled gout
    Additional relevant MeSH terms:
    Gout
    Methotrexate

    Study Results

    No Results Posted as of Apr 4, 2022