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
- Registration Number
- NCT06229145
- Lead Sponsor
- Amgen
- 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.
- Detailed Description
Acquired from Horizon in 2024.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 262
-
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.
- 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
- Diagnosis of osteomyelitis
- Known history of hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome
- A known intolerance to all protocol-standard gout flare prophylaxis regimens (i.e., participant must be able to tolerate at least 1 of the following: colchicine and/or non-steroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day)
- Current pulmonary fibrosis, bronchiectasis or interstitial pneumonitis. If deemed necessary by the Investigator, a chest X-ray may be performed during Screening.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pegloticase + Methotrexate Q2W Pegloticase 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. Pegloticase + Methotrexate Q2W Methotrexate 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. Pegloticase + Methotrexate Q4W Pegloticase 16 mg pegloticase will be administered intravenously every 4 weeks for 24 weeks during double blind treatment and 24 weeks during open label. Pegloticase + Methotrexate Q4W Methotrexate 16 mg pegloticase will be administered intravenously every 4 weeks for 24 weeks during double blind treatment and 24 weeks during open label.
- Primary Outcome Measures
Name Time Method Proportion of Participants achieving and maintaining serum uric acid (sUA) < 6 mg/dL at least 80% of the time Month 6
- Secondary Outcome Measures
Name Time Method Proportion of Participants with complete resolution of ≥ 1 tophus Week 24
Trial Locations
- Locations (69)
The University of Alabama at Birmingham (UAB)
🇺🇸Birmingham, Alabama, United States
Orthopedic Physicians Alaska - Rheumatology and Infusion
🇺🇸Anchorage, Alaska, United States
Arizona Arthritis and Rheumatology
🇺🇸Tucson, Arizona, United States
Arizona Arthritis and Rheumatology Rese
🇺🇸Flagstaff, Arizona, United States
Arizona Arthritis & Rheumatology
🇺🇸Sun City, Arizona, United States
Arizona ArthritisRheumatology Resea
🇺🇸Mesa, Arizona, United States
Arizona Arthritis and Rheumatology Research
🇺🇸Phoenix, Arizona, United States
Covina Arthritis Clinic
🇺🇸Covina, California, United States
Medvin Clinical Research- Riverside
🇺🇸Hemet, California, United States
TriWest Research Associates
🇺🇸San Diego, California, United States
PCCRS
🇺🇸San Leandro, California, United States
Saint John's Health Center
🇺🇸Santa Monica, California, United States
C.V. Mehta MD Medical Corporation
🇺🇸Temecula, California, United States
Foothill Arthritis
🇺🇸Tujunga, California, United States
Medvin Clinical Research
🇺🇸Whittier, California, United States
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
Lynn Institute of the Rockies
🇺🇸Colorado Springs, Colorado, United States
Denver Arthritis Clinic
🇺🇸Denver, Colorado, United States
Arthritis & Rheumatic Disease
🇺🇸Aventura, Florida, United States
Prohealth Research Center
🇺🇸Doral, Florida, United States
Homestead Associates in Research,Inc
🇺🇸Homestead, Florida, United States
Life Clinical Trials
🇺🇸Margate, Florida, United States
D&H National Research Centers, Inc.
🇺🇸Miami, Florida, United States
Well Pharma
🇺🇸Miami, Florida, United States
Felicidad Medical Research, LLC.
🇺🇸Miami, Florida, United States
New Generation Of Medical Research
🇺🇸Naples, Florida, United States
IRIS Research & Development
🇺🇸Plantation, Florida, United States
D&H Pompano Research Center
🇺🇸Pompano Beach, Florida, United States
D&H Tamarac Research Center
🇺🇸Tamarac, Florida, United States
ClinPro Research Solutions, LLC
🇺🇸Tampa, Florida, United States
GCP Clinical Research
🇺🇸Tampa, Florida, United States
Conquest Research
🇺🇸Winter Park, Florida, United States
Arthritis Center of North Georgia
🇺🇸Gainesville, Georgia, United States
Vista Clinical Research, LLC
🇺🇸Newnan, Georgia, United States
Velocity Clinical Research - Boise
🇺🇸Meridian, Idaho, United States
Great Lakes Clin. Trials
🇺🇸Chicago, Illinois, United States
Great Lakes Clinical Trials - Gurnee
🇺🇸Gurnee, Illinois, United States
Crowley CORE
🇺🇸Hinsdale, Illinois, United States
Lake Cumberland Rheumatology, PLLC
🇺🇸New Albany, Indiana, United States
L-MARC Research Center
🇺🇸Louisville, Kentucky, United States
Velocity CR - New Orleans
🇺🇸New Orleans, Louisiana, United States
Michigan Medicine
🇺🇸Ann Arbor, Michigan, United States
June DO, PC
🇺🇸Lansing, Michigan, United States
Clinical Research Institute of Michigan, LLC
🇺🇸Saint Clair Shores, Michigan, United States
Inspire Santa Fe Medical Group
🇺🇸Santa Fe, New Mexico, United States
Velocity Clinical Research-Vestal
🇺🇸Vestal, New York, United States
OnSite Clinical Solutions, LLC
🇺🇸Charlotte, North Carolina, United States
Research Carolina Elite, LLC
🇺🇸Denver, North Carolina, United States
Triad Clinical Trials
🇺🇸Greensboro, North Carolina, United States
Accellacare of Hickory
🇺🇸Hickory, North Carolina, United States
Cape Fear Arthritis Care
🇺🇸Leland, North Carolina, United States
Shelby Clinical Research
🇺🇸Shelby, North Carolina, United States
Velocity Clinical Res, Cleveland
🇺🇸Beachwood, Ohio, United States
Velocity Clinical Research - Cincinnati
🇺🇸Cincinnati, Ohio, United States
Lynn Health Science Institute
🇺🇸Oklahoma City, Oklahoma, United States
Altoona Center for Clinical Research - Research
🇺🇸Duncansville, Pennsylvania, United States
Velocity Clinical Research, Greenville
🇺🇸Greenville, South Carolina, United States
Premier Clinics Pa
🇺🇸Rock Hill, South Carolina, United States
Low Country Rheumatology
🇺🇸Summerville, South Carolina, United States
Amarillo Center for Clinical Research, Ltd.
🇺🇸Amarillo, Texas, United States
Synergy Groups Medical LLC
🇺🇸Houston, Texas, United States
Clinical Trial Network
🇺🇸Houston, Texas, United States
Pioneer Research Solutions, Inc.
🇺🇸Houston, Texas, United States
AIM Trials - Internal Medicine
🇺🇸Plano, Texas, United States
Clinical Trials of Texas, Inc.
🇺🇸San Antonio, Texas, United States
Siena Research Network
🇺🇸Sugar Land, Texas, United States
Velocity Clinical Research - Salt Lake City
🇺🇸West Jordan, Utah, United States
Velocity Clin Research-Portsmouth
🇺🇸Suffolk, Virginia, United States
Arthritis Northwest, PLLC - Research
🇺🇸Spokane, Washington, United States