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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Chronic Uncontrolled Gout, Gout, Uncontrolled Gout

Intervention / Treatment
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* Biological: Pegloticase with MTX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult men or women ≥18 years of age. 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 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: Severe chronic or recurrent bacterial infections, such as recurrent pneumonia or chronic bronchiectasis. 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. Glucose-6-phosphate dehydrogenase (G6PD) deficiency (tested at Screening Visit). 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. 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. 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. Prior treatment with pegloticase (KRYSTEXXA), another recombinant uricase (rasburicase), or concomitant therapy with a polyethylene glycol-conjugated drug. Currently receiving systemic or radiologic treatment for ongoing cancer. History of malignancy within 5 years other than non-melanoma skin cancer or in situ carcinoma of cervix.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Three different infusion durations may be used. 60-minute infusion, 45-minute infusion and 30-minute.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pegloticase 60 Minute Infusion with methotrexate (MTX)<br>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<br>* Participants will receive MTX during the run-in period then pegloticase with MTX for up to 24 weeks during the treatment period<br>* Other names: Methotrexate;|
| Experimental: Pegloticase 45 Minute Infusion with methotrexate (MTX)<br>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<br>* Participants will receive MTX during the run-in period then pegloticase with MTX for up to 24 weeks during the treatment period<br>* Other names: Methotrexate;|
| Experimental: Pegloticase 30 Minute Infusion with methotrexate (MTX)<br>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<br>* Participants will receive MTX during the run-in period then pegloticase with MTX for up to 24 weeks during the treatment period<br>* Other names: Methotrexate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of participants experiencing Infusion Reactions (IRs), including anaphylaxis related to pegloticase |  | Day 1 through Week 24. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6 | Responders are defined as participants achieving and maintaining sUA < 6 mg/dL for at least 80% of the time during Month 6. Participants meeting the sUA discontinuation criteria (pre-infusion sUA >6 mg/dL at 2 consecutive scheduled trial visits beginning with the Week 2 Visit) were counted as non-responders. | Month 6 (Weeks 20, 22, 24) | 
| The proportion of participants who experienced any of the following events: IR leading to discontinuation of treatment, anaphylaxis, or meeting Individual participant sUA Discontinuation Criteria. | 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, and continues on the study. | Day 1 to Week 24 | 
| Time to any of the following events: IR leading to discontinuation of treatment, anaphylaxis, or meeting individual participant sUA Discontinuation Criteria (two consecutive pre-infusion sUAs > 6mg/dL). | 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, and continues on the study. | Day 1 to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gout, uncontrolled gout