Study of Pegloticase (KRYSTEXXA®) Plus Methotrexate in Patients With Uncontrolled Gout
NCT ID: NCT03635957
Last Updated: 2024-06-26
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE4
14 participants
INTERVENTIONAL
2018-09-26
2020-10-26
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Study of KRYSTEXXA® (Pegloticase) Plus Methotrexate in Participants With Uncontrolled Gout
NCT03994731
A Phase 4, Open-label Study of KRYSTEXXA® (Pegloticase) Co-administered With Methotrexate (MTX) in Patients With Uncontrolled Gout (FORWARD OL)
NCT04762498
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
Pegloticase and Methotrexate Co-administered in Participants With Uncontrolled Gout Who Previously Failed Pegloticase Monotherapy
NCT04772313
Infusion Duration Study To Assess Tolerability of Pegloticase Administered With a Shorter Infusion Duration in Subjects With Uncontrolled Gout Receiving Methotrexate
NCT04511702
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Study acquired from Horizon in 2024.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Pegloticase With Methotrexate (MTX)
Run-In Period: oral MTX at a dose of 15 mg weekly for 4 weeks prior to the first dose of pegloticase.
Pegloticase + Immunomodulator (IMM) Period: pegloticase 8 mg administered intravenously (IV) every 2 weeks from Day 1 through the Week 50 Visit for a total of 26 infusions. MTX 15 mg weekly on the same day each week, within 1 to 3 days prior to each pegloticase infusion and one additional weekly dose after the last infusion.
Pegloticase
pegloticase administered intravenously (IV)
Methotrexate (MTX)
oral MTX
Standard Gout Flare Prophylaxis
It is required that before a subject begins the Pegloticase + IMM Period, he or she has been taking at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day) for ≥1 week before the first dose of pegloticase and continues flare prophylaxis per American College of Rheumatology guidelines \[Khanna D et al.2012\] for the greater of 1) 6 months, 2) 3 months after achieving target serum urate (sUA \< 6 mg/dL) for patients with no tophi detected on physical exam, or 3) 6 months after achieving target serum urate (sUA \< 5 mg/dL) for patients with one or more tophi detected on initial physical exam that have since resolved.
Infusion Reaction (IR) Prophylaxis
For IR prophylaxis, fexofenadine (60 mg or 180 mg orally based on the Principal Investigator's discretion) will be taken the day before each infusion; fexofenadine (60 mg or 180 mg orally based on the Principal Investigator's discretion) and acetaminophen (1000 mg orally) will be taken the morning of each infusion; and methylprednisolone (125 mg IV) given over the infusion duration 10-30 minutes (recommended) or hydrocortisone (200 mg IV) will be administered immediately prior to each infusion.
Folic Acid
Subjects will also take folic acid 1 mg orally every day beginning at Week -4 (the start of MTX) and continuing until prior to the Week 52 Visit.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Pegloticase
pegloticase administered intravenously (IV)
Methotrexate (MTX)
oral MTX
Standard Gout Flare Prophylaxis
It is required that before a subject begins the Pegloticase + IMM Period, he or she has been taking at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day) for ≥1 week before the first dose of pegloticase and continues flare prophylaxis per American College of Rheumatology guidelines \[Khanna D et al.2012\] for the greater of 1) 6 months, 2) 3 months after achieving target serum urate (sUA \< 6 mg/dL) for patients with no tophi detected on physical exam, or 3) 6 months after achieving target serum urate (sUA \< 5 mg/dL) for patients with one or more tophi detected on initial physical exam that have since resolved.
Infusion Reaction (IR) Prophylaxis
For IR prophylaxis, fexofenadine (60 mg or 180 mg orally based on the Principal Investigator's discretion) will be taken the day before each infusion; fexofenadine (60 mg or 180 mg orally based on the Principal Investigator's discretion) and acetaminophen (1000 mg orally) will be taken the morning of each infusion; and methylprednisolone (125 mg IV) given over the infusion duration 10-30 minutes (recommended) or hydrocortisone (200 mg IV) will be administered immediately prior to each infusion.
Folic Acid
Subjects will also take folic acid 1 mg orally every day beginning at Week -4 (the start of MTX) and continuing until prior to the Week 52 Visit.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the study.
3. Adult men or women ≥18 to ≤65 years of age.
4. 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 the Screening/(methotrexate) MTX Run in Period; participants 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 -4 (start of MTX dosing) and continue for 30 days after the last dose of pegloticase or at least one ovulatory cycle after the last dose of MTX (whichever is the longest duration after the last dose of pegloticase or 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.
5. Men who are not vasectomized must not impregnant their female partner during the study and for at least 3 months after the last dose of MTX.
6. Hyperuricemia at the Screening, Week -4, or Week -2 Visit of the Screening/MTX Run in Period, as documented by sUA ≥6 mg/dL.
7. Uncontrolled gout, defined as meeting the following criteria:
serum uric acid (sUA) ≥6 mg/dL prior to entry into the pegloticase +IMM Period (any laboratory tests during screening up to and including during the MTX Run in Period) and at least 1 of the following: inability to maintain sUA \<6 mg/dL on other urate-lowering therapy; intolerable side effects associated with current urate-lowering therapy; functionally limiting tophaceous deposits (including those detected clinically or by dual-energy computed tomography \[DECT\] imaging)
8. Able to tolerate MTX 15 mg for 4 weeks during the MTX Run-in Period prior to the first dose of pegloticase.
Exclusion Criteria
2. Any serious acute bacterial infection, unless treated and completely resolved with antibiotics at least 2 weeks prior to the Week -4 Visit of the MTX Run-in Period.
3. Severe chronic or recurrent bacterial infections, such as recurrent pneumonia or chronic bronchiectasis.
4. Current immunocompromised condition, including current or chronic treatment with systemic immunosuppressive agents, including prednisone \>10 mg/day or equivalent dose of other corticosteroid.
5. History of any transplant surgery requiring maintenance immunosuppressive therapy.
6. Known history of hepatitis B virus surface antigen positivity or hepatitis B DNA positivity.
7. Known history of hepatitis C virus RNA positivity.
8. Human immunodeficiency virus (HIV) positivity (tested at the Screening Visit).
9. Glucose-6-phosphate dehydrogenase (G6PD) deficiency (tested at the Screening Visit).
10. Severe chronic renal impairment (glomerular filtration rate \<25 mL/min/1.73 m\^2) or currently on dialysis.
11. 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) at the end of the Screening/MTX Run-in Period.
12. Pregnant, planning to become pregnant, breastfeeding, planning to impregnant female partner, or not on an effective form of birth control, as determined by the Investigator.
13. Prior treatment with pegloticase (KRYSTEXXA®), another recombinant uricase (rasburicase), or concomitant therapy with a polyethylene glycol-conjugated drug.
14. Known allergy to pegylated products or history of anaphylactic reaction to a recombinant protein or porcine product.
15. Contraindication to MTX treatment or MTX treatment considered inappropriate.
16. Known intolerance to MTX.
17. Receipt of an investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to MTX administration at Week -4 or plans to take an investigational drug during the study.
18. Current liver disease, as determined by alanine transaminase or aspartate transaminase levels \>3 times upper limit of normal at the Screening Visit.
19. Currently receiving systemic or radiologic treatment for ongoing cancer, excluding non melanoma skin cancer.
20. History of malignancy within 5 years other than non-melanoma skin cancer or in situ carcinoma of cervix.
21. Uncontrolled hyperglycemia with a plasma glucose value \>240 mg/dL at screening that is not subsequently controlled by the end of the Screening/MTX Run-in Period.
22. Diagnosis of osteomyelitis.
23. Known history of hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome.
24. 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 participant or interfere with the participant's ability to comply with the protocol requirements or complete the study.
25. Alcohol use in excess of 3 alcoholic beverages per week.
26. Currently receiving allopurinol and unable to discontinue medication 7 days prior to MTX dosing at Week -4 and unable to discontinue treatment during the duration of the study.
18 Years
65 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Amgen
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
MD
Role: STUDY_DIRECTOR
Amgen
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Orthopedic Physicians Alaska
Anchorage, Alaska, United States
Arizona Arthritis & Rheumatology -West Valley
Glendale, Arizona, United States
Arizona Arthritis & Rheumatology -East Valley
Mesa, Arizona, United States
Avail Clinical Research
DeLand, Florida, United States
Western Washington Arthritis Clinic
Bothell, Washington, United States
Arthritis Northwest PLLC
Spokane, Washington, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Botson JK, Obermeyer K, LaMoreaux B, Zhao L, Weinblatt ME, Peterson J. Improved joint and patient-reported health assessments with pegloticase plus methotrexate co-therapy in patients with uncontrolled gout: 12-month exploratory outcomes of the MIRROR open-label trial. Arthritis Res Ther. 2022 Dec 27;24(1):281. doi: 10.1186/s13075-022-02979-4.
Botson JK, Tesser JRP, Bennett R, Kenney HM, Peloso PM, Obermeyer K, Song Y, LaMoreaux B, Zhao L, Xin Y, Chamberlain J, Ramanathan S, Weinblatt ME, Peterson J. A multicentre, efficacy and safety study of methotrexate to increase response rates in patients with uncontrolled gout receiving pegloticase (MIRROR): 12-month efficacy, safety, immunogenicity, and pharmacokinetic findings during long-term extension of an open-label study. Arthritis Res Ther. 2022 Aug 25;24(1):208. doi: 10.1186/s13075-022-02865-z.
Dalbeth N, Becce F, Botson JK, Zhao L, Kumar A. Dual-energy CT assessment of rapid monosodium urate depletion and bone erosion remodelling during pegloticase plus methotrexate co-therapy. Rheumatology (Oxford). 2022 Nov 28;61(12):4898-4904. doi: 10.1093/rheumatology/keac173.
Botson JK, Tesser JRP, Bennett R, Kenney HM, Peloso PM, Obermeyer K, LaMoreaux B, Weinblatt ME, Peterson J. Pegloticase in Combination With Methotrexate in Patients With Uncontrolled Gout: A Multicenter, Open-label Study (MIRROR). J Rheumatol. 2021 May;48(5):767-774. doi: 10.3899/jrheum.200460. Epub 2020 Sep 15.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
HZNP-KRY-201
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.