Study of KRYSTEXXA® (Pegloticase) Plus Methotrexate in Participants With Uncontrolled Gout

Completed · Phase 4 · Has a placebo group

Conditions studied: Gout

In brief

The purpose of this study is to assess the potential for pegloticase with methotrexate (MTX) to increase the response rate seen with pegloticase alone, and to characterize the safety, tolerability and pharmacokinetics (PK) of the concomitant use of pegloticase with MTX, by comparing pegloticase co-administered with MTX to pegloticase co-administered with placebo for MTX in adults with uncontrolled gout.

Key facts

Study ID: NCT03994731
Run by: Amgen
People needed: 152
Starts: 2019-06-13
Expected to finish: 2022-04-11
Last updated by the study team: 2024-06-26

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Willing and able to give informed consent.
Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the study.
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 subject interview, and;
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 any oral urate lowering therapy for at least 7 days prior to MTX dosing at Week -6 and remain off when receiving pegloticase infusions.
Women of childbearing potential (including those with an onset of menopause <2 years prior to screening, non-therapy-induced amenorrhea for <12 months prior to screening, or not surgically sterile [absence of ovaries and/or uterus]) must have negative serum/urine pregnancy tests during Screening and Week -6; subjects must agree to use 2 reliable forms of contraception during the study, one of which is recommended to be hormonal, such as an oral contraceptive. Hormonal contraception must be started ≥1 full cycle prior to Week -6 (start of MTX) and continue for 30 days after the last dose of pegloticase, or at least one ovulatory cycle after the last dose of MTX or placebo for MTX (whichever is the longest duration after the last dose of pegloticase or MTX or placebo for MTX). Highly effective contraceptive methods (with a failure rate <1% per year), when used consistently and correctly, include implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence, or vasectomized partner.
Men who are not vasectomized must agree to use appropriate contraception so as to not impregnate a female partner of reproductive potential during the study, beginning with the initiation of MTX at Week -6 and continuing and for at least 3 months after the last dose of MTX or placebo for MTX.
Able to tolerate MTX 15 mg orally for 2 weeks (Week -6 through Week -4) prior to randomization.

You may not qualify if…

Weight >160 kg (352 pounds) at Screening.
Any serious acute bacterial infection, unless treated and completely resolved with antibiotics at least 2 weeks prior to the Week -6 Visit.
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) would also meet exclusion criteria.
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 ribonucleic acid (RNA) positivity.
Known history of Human Immunodeficiency Virus (HIV) positivity.
Glucose-6-phosphate dehydrogenase deficiency (tested at the Screening Visit).
Chronic renal impairment defined as estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73 m\^2 or currently on dialysis.
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 Randomization at 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 polyethylene glycol-conjugated drug.
Known allergy to pegylated products or history of anaphylactic reaction to a recombinant protein or porcine product.
Contraindication to MTX treatment or MTX treatment considered inappropriate.
Known intolerance to MTX.
Receipt of an investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to MTX administration at Week -6 or plans to take an investigational drug during the study.
Liver transaminase levels (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) > upper limit of normal (ULN) or albumin < the lower limit of normal (LLN) at the Screening Visit).
Chronic liver disease.
White blood cell count < 4,000/µL, hematocrit < 32 percent, 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.
Unsuitable candidate for the study, based on the opinion of the Investigator (e.g., cognitive impairment), such that participation might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements or complete the study.

Where it is running

Orthopedic Physicians Alaska — Anchorage, Alaska, United States
Arizona Arthritis and Rheumatology Research, PLLC - Flagstaff — Flagstaff, Arizona, United States
Arizona Arthritis and Rheumatology Research, PLLC-West — Glendale, Arizona, United States
Arizona Arthritis and Rheumatology Research, PLLC-East — Mesa, Arizona, United States
Applied Research Center of Arkansas, Inc — Little Rock, Arkansas, United States
TriWest Research Associates — El Cajon, California, United States
Advanced Investigative Medicine, Inc. — Hawthorne, California, United States
Axis Clinical Trials — Los Angeles, California, United States
ACRC Studies — Poway, California, United States
ClinEdge Sierra Rheumatology, Inc. — Roseville, California, United States
East Bay Rheumatology Medical Group, Inc. — San Leandro, California, United States
Providence St. John's Health Clinic — Santa Monica, California, United States
Medvin Clinical Research — Tujunga, California, United States
San Fernando Valley Health Institute — Van Nuys, California, United States
Ventura Clinical Trials — Ventura, California, United States
University of Colorado Division of Rheumatology — Aurora, Colorado, United States
Denver Arthritis Clinic — Denver, Colorado, United States
Avail Clinical Research — DeLand, Florida, United States
Prohealth Research Center — Doral, Florida, United States
Omega Research Maitland — Orlando, Florida, United States
DMI Research — Pinellas Park, Florida, United States
Napa Research Center — Pompano Beach, Florida, United States
GCP Clinical Research — Tampa, Florida, United States
Florida Medical Clinic, LLC — Zephyrhills, Florida, United States
University of Alabama — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.