A Trial to Investigate the Non-inferiority of Pegloticase Administered Every 4 Weeks (Q4W) With MTX Compared With Every 2 Weeks (Q2W) With MTX in Participants With Uncontrolled Refractory Gout

NCT06229145 | Completed Phase 4 FDA Drug

• 1 other identifier: HZNP-KRY-409
• Study Type: interventional
• Target: 262
• Locations: 1 country
• Sites: 74

Brief Summary

The study consists of 24-week double-blind trial to evaluate the non-inferiority of the efficacy and safety of pegloticase Q4W with MTX versus pegloticase Q2W with MTX, followed by a 24-week open-label extension of pegloticase Q4W with MTX, in participants with uncontrolled refractory gout. The main objective of the study is to evaluate the effect of pegloticase 16 mg administered Q4W with MTX versus pegloticase 8 mg administered Q2W with MTX, on the response rate during Month 6, as measured by the sustained normalization of sUA to \< 6 mg/dL for at least 80% of the time.

Conditions

Gout

Keywords

Uncontrolled Gout; pegloticase; Krystexxa; Methotrexate; Chronic Gout

Outcome Measures

Primary Outcomes (1)

• Evaluate the effect of pegloticase 16 mg administered Q4W with MTX versus pegloticase 8 mg administered Q2W with MTX, on the response rate as measured by the sustained normalization of sUA to < 6 mg/dL for at least 80% of the time

  Proportion of participants achieving and maintaining serum uric acid (sUA) \< 6 mg/dL at least 80% of the time

  Month 6

Secondary Outcomes (1)

• Evaluate the effect of pegloticase 16 mg Q4W with MTX compared with pegloticase 8 mg Q2W with MTX on tophi resolution

  Week 24

Study Arms (2)

Pegloticase + Methotrexate Q4W

EXPERIMENTAL

16 mg pegloticase will be administered intravenously every 4 weeks for 24 weeks during double blind treatment and 24 weeks during open label.

Biological: Pegloticase; Drug: Methotrexate

Pegloticase + Methotrexate Q2W

EXPERIMENTAL

8 mg pegloticase will be administered intravenously every 2 weeks for 24 weeks during double blind treatment and 16 mg pegloticase every 4 weeks for 24 weeks during open label.

Biological: Pegloticase; Drug: Methotrexate

Interventions

Pegloticase BIOLOGICAL

IV infusion

Also known as: Krystexxa

Pegloticase + Methotrexate Q2W; Pegloticase + Methotrexate Q4W

Methotrexate DRUG

Oral

Pegloticase + Methotrexate Q2W; Pegloticase + Methotrexate Q4W

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult men or women ≥ 18 years of age
• Uncontrolled gout, defined as meeting the following criteria:
• Hyperuricemia during the Screening Period, defined as sUA ≥ 7 mg/dL, and;
• Failure to maintain normalization of sUA with xanthine oxidase inhibitors at the maximum medically appropriate dose, or with a contraindication to xanthine oxidase inhibitor therapy based on medical record review or participant interview, and;
• Symptoms of gout
• Willing to discontinue any oral ULT for at least 7 days prior to MTX dosing at Week -4 and continue not receiving any oral ULT when receiving pegloticase/placebo for pegloticase infusions
• Women of childbearing potential must have negative serum/urine pregnancy tests during screening and Week -4.
• Men who are not vasectomized must agree to use appropriate contraception, so as to not impregnate a female partner of reproductive potential during the trial.

You may not qualify if:

• 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 (3 months or longer)
• History of any transplant surgery requiring maintenance immunosuppressive therapy
• Known history of hepatitis B virus surface antigen positivity or hepatitis B DNA positivity
• Known history of hepatitis C virus RNA positivity, unless treated and viral load is negative
• Known history of human immunodeficiency virus (HIV) positivity
• G6PD deficiency (quantitative test at the Screening Visit centrally or locally)
• Non-compensated congestive heart failure or hospitalization for congestive heart failure within 3 months of the Screening Visit, uncontrolled arrhythmia, treatment for acute coronary syndrome (myocardial infarction or unstable angina) or uncontrolled blood pressure (\> 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, another recombinant uricase (rasburicase) or concomitant therapy with a PEG-conjugated drug
• Unable to tolerate MTX 15 mg orally during the MTX Run-in Period
• Chronic liver disease
• White blood cell count \< 4,000/μL, hematocrit \< 32% or platelet count \< 75,000/μL
• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (74)

The University of Alabama at Birmingham (UAB)

Birmingham, Alabama, 35233, United States

Location

Orthopedic Physicians Alaska - Rheumatology and Infusion

Anchorage, Alaska, 99508-5234, United States

Location

Arizona Arthritis and Rheumatology Associates - Chandler

Chandler, Arizona, 85225-2915, United States

Location

Arizona Arthritis and Rheumatology Rese

Flagstaff, Arizona, 86001, United States

Location

Arizona Arthritis & Rheumatology Research, PLLC

Gilbert, Arizona, 85297, United States

Location

Arizona Arthritis & Rheumatology Research, PLLC

Mesa, Arizona, 85032, United States

Location

Arizona Arthritis and Rheumatology Research, PLLC

Mesa, Arizona, 85210, United States

Location

Arizona Arthritis and Rheumatology Research, PLLC

Phoenix, Arizona, 85037-4403, United States

Location

Arizona Arthritis and Rheumatology Research

Phoenix, Arizona, 85037, United States

Location

Arizona Arthritis & Rheumatology Research, PLLC

Sun City, Arizona, 85351, United States

Location

Arizona Arthritis and Rheumatology

Tucson, Arizona, 85704, United States

Location

Covina Arthritis Clinic

Covina, California, 91722, United States

Location

Medvin Clinical Research- Riverside

Hemet, California, 92543, United States

Location

Velocity Clinical Research - Boise - ERN - PPDS

North Hollywood, California, 83642, United States

Location

TriWest Research Associates

San Diego, California, 92108, United States

Location

Precision Comprehensive Clinical Research Solutions

San Leandro, California, 94578-2630, United States

Location

Saint John's Health Center - Providence St John's Health Ctr

Santa Monica, California, 90404, United States

Location

C.V. Mehta MD Medical Corporation

Temecula, California, 92592, United States

Location

Foothill Arthritis

Tujunga, California, 91042, United States

Location

Medvin Clinical Research

Whittier, California, 90602, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Lynn Institute of the Rockies

Colorado Springs, Colorado, 80918, United States

Location

Denver Arthritis Clinic - Rheumatology

Denver, Colorado, 80230, United States

Location

Arthritis & Rheumatic Disease

Aventura, Florida, 33180-1204, United States

Location

Prohealth Research Center

Doral, Florida, 33166, United States

Location

Life Clinical Trials

Margate, Florida, 33063-5675, United States

Location

Homestead Associates in Research,Inc

Miami, Florida, 33032-8225, United States

Location

D&H National Research Centers, Inc.

Miami, Florida, 33155, United States

Location

Well Pharma

Miami, Florida, 33173, United States

Location

Felicidad Medical Research, LLC.

Miami, Florida, 33184, United States

Location

New Generation Of Medical Research

Naples, Florida, 34104, United States

Location

IRIS Research & Development

Plantation, Florida, 33324, United States

Location

D&H Pompano Research Center

Pompano Beach, Florida, 33064, United States

Location

D&H Tamarac Research Center

Tamarac, Florida, 33321, United States

Location

GCP Clinical Research

Tampa, Florida, 33609, United States

Location

ClinPro Research Solutions, LLC

Tampa, Florida, 33613, United States

Location

Arthritis Center of North Georgia

Gainesville, Georgia, 30501, United States

Location

Vista Clinical Research, LLC

Newnan, Georgia, 30265, United States

Location

Great Lakes Clin. Trials

Chicago, Illinois, 60625, United States

Location

Conquest Research - Anesthesiology/Pain Medicine

Chicago, Illinois, 60637, United States

Location

Great Lakes Clinical Trials - Gurnee

Highland Park, Illinois, 60035, United States

Location

Crowley CORE - Illinois Bone and Joint Institute

Hinsdale, Illinois, 60521, United States

Location

Lake Cumberland Rheumatology, PLLC

New Albany, Indiana, 47150, United States

Location

L-MARC Research Center

Louisville, Kentucky, 40213, United States

Location

Velocity CR - New Orleans

Covington, Louisiana, 70433, United States

Location

Velocity CR - New Orleans

New Orleans, Louisiana, 70121-2429, United States

Location

Michigan Medicine

Ann Arbor, Michigan, 48109, United States

Location

June DO,PC

Lansing, Michigan, 48911, United States

Location

Clinical Research Institute of Michigan, LLC

Saint Clair Shores, Michigan, 48081, United States

Location

Inspire Santa Fe Medical Group

Santa Fe, New Mexico, 87505, United States

Location

Velocity Clinical Research-Vestal

Vestal, New York, 13850, United States

Location

OnSite Clinical Solutions, LLC

Charlotte, North Carolina, 28226, United States

Location

Research Carolina Elite

Denver, North Carolina, 28037, United States

Location

Triad Clinical Trials - Gastroenterology

Greensboro, North Carolina, 27410, United States

Location

Accellacare of Hickory

Hickory, North Carolina, 28602, United States

Location

Cape Fear Arthritis Care

Leland, North Carolina, 28451-4168, United States

Location

Shelby Clinical Research - Family Medicine

Shelby, North Carolina, 28152, United States

Location

Velocity Clinical Research- Cincinatti

Cincinnati, Ohio, 45242, United States

Location

Velocity Clinical Research - Cleveland

Cleveland, Ohio, 44122, United States

Location

Lynn Health Science Institute

Oklahoma City, Oklahoma, 73111-3324, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Velocity Clinical Research, Spartanburg - Pulmonology

Greenville, South Carolina, 29615, United States

Location

Premier Clinics Pa - Rock Hill, Sc

Rock Hill, South Carolina, 29732, United States

Location

Low Country Rheumatology

Summerville, South Carolina, 29486-7887, United States

Location

Amarillo Center for Clinical Research, Ltd.

Amarillo, Texas, 79124, United States

Location

Clinical Trial Network

Austin, Texas, 78750, United States

Location

Synergy Groups Medical LLC

Houston, Texas, 77061, United States

Location

Pioneer Research Solutions, Inc.

Houston, Texas, 77099, United States

Location

AIM Trials - Internal Medicine

Plano, Texas, 75093, United States

Location

Clinical Trials of Texas, Inc.

San Antonio, Texas, 78229, United States

Location

Texas Research Center

Sugar Land, Texas, 77479, United States

Location

Velocity Clinical Research - Salt Lake City (West Jordan)

West Jordan, Utah, 84088, United States

Location

Velocity Clinical Research-Portsmouth

Portsmouth, Virginia, 23703-3200, United States

Location

Arthritis Northwest, PLLC - Research

Spokane, Washington, 99204, United States

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Gout

Interventions

Pegloticase; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2024
• First Posted: January 29, 2024
• Study Start: March 18, 2024
• Primary Completion: July 30, 2025
• Study Completion: March 11, 2026
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

US (74)