GoutPhase 4NCT06229145
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
A Phase 4 study testing Pegloticase and Methotrexate in people with Gout, run by Amgen at 74 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gout
- What is being tested?
- Pegloticase and Methotrexate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 306 participants
- Where
- 74 sitesUnited States
- Study dates
- 18 Mar 2024to 26 Mar 2026
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
74 sites in 1 country.
74 sites in 1 country
United States74 sites
Amarillo Center for Clinical Research, Ltd.
Amarillo, Texas, 79124
Orthopedic Physicians Alaska - Rheumatology and Infusion
Anchorage, Alaska, 99508-5234
Michigan Medicine
Ann Arbor, Michigan, 48109
University of Colorado Denver
Aurora, Colorado, 80045
Clinical Trial Network
Austin, Texas, 78750
Arthritis & Rheumatic Disease
Aventura, Florida, 33180-1204
The University of Alabama at Birmingham (UAB)
Birmingham, Alabama, 35233
Arizona Arthritis and Rheumatology Associates - Chandler
Chandler, Arizona, 85225-2915
OnSite Clinical Solutions, LLC
Charlotte, North Carolina, 28226
Great Lakes Clin. Trials
Chicago, Illinois, 60625
Conquest Research - Anesthesiology/Pain Medicine
Chicago, Illinois, 60637
Velocity Clinical Research- Cincinatti
Cincinnati, Ohio, 45242
Velocity Clinical Research - Cleveland
Cleveland, Ohio, 44122
Lynn Institute of the Rockies
Colorado Springs, Colorado, 80918
Covina Arthritis Clinic
Covina, California, 91722
Velocity CR - New Orleans
Covington, Louisiana, 70433
Denver Arthritis Clinic - Rheumatology
Denver, Colorado, 80230
Research Carolina Elite
Denver, North Carolina, 28037
Prohealth Research Center
Doral, Florida, 33166
Altoona Center for Clinical Research
Duncansville, Pennsylvania, 16635
Arizona Arthritis and Rheumatology Rese
Flagstaff, Arizona, 86001
Arthritis Center of North Georgia
Gainesville, Georgia, 30501
Arizona Arthritis & Rheumatology Research, PLLC
Gilbert, Arizona, 85297
Triad Clinical Trials - Gastroenterology
Greensboro, North Carolina, 27410
Velocity Clinical Research, Spartanburg - Pulmonology
Greenville, South Carolina, 29615
Medvin Clinical Research- Riverside
Hemet, California, 92543
Accellacare of Hickory
Hickory, North Carolina, 28602
Great Lakes Clinical Trials - Gurnee
Highland Park, Illinois, 60035
Crowley CORE - Illinois Bone and Joint Institute
Hinsdale, Illinois, 60521
Synergy Groups Medical LLC
Houston, Texas, 77061
Pioneer Research Solutions, Inc.
Houston, Texas, 77099
June DO,PC
Lansing, Michigan, 48911
Cape Fear Arthritis Care
Leland, North Carolina, 28451-4168
L-MARC Research Center
Louisville, Kentucky, 40213
Life Clinical Trials
Margate, Florida, 33063-5675
Arizona Arthritis & Rheumatology Research, PLLC
Mesa, Arizona, 85032
Arizona Arthritis and Rheumatology Research, PLLC
Mesa, Arizona, 85210
Homestead Associates in Research,Inc
Miami, Florida, 33032-8225
D&H National Research Centers, Inc.
Miami, Florida, 33155
Well Pharma
Miami, Florida, 33173
Felicidad Medical Research, LLC.
Miami, Florida, 33184
New Generation Of Medical Research
Naples, Florida, 34104
Lake Cumberland Rheumatology, PLLC
New Albany, Indiana, 47150
Velocity CR - New Orleans
New Orleans, Louisiana, 70121-2429
Vista Clinical Research, LLC
Newnan, Georgia, 30265
Velocity Clinical Research - Boise - ERN - PPDS
North Hollywood, California, 83642
Lynn Health Science Institute
Oklahoma City, Oklahoma, 73111-3324
Arizona Arthritis and Rheumatology Research, PLLC
Phoenix, Arizona, 85037-4403
Arizona Arthritis and Rheumatology Research
Phoenix, Arizona, 85037
AIM Trials - Internal Medicine
Plano, Texas, 75093
IRIS Research & Development
Plantation, Florida, 33324
D&H Pompano Research Center
Pompano Beach, Florida, 33064
Velocity Clinical Research-Portsmouth
Portsmouth, Virginia, 23703-3200
Premier Clinics Pa - Rock Hill, Sc
Rock Hill, South Carolina, 29732
Clinical Research Institute of Michigan, LLC
Saint Clair Shores, Michigan, 48081
Clinical Trials of Texas, Inc.
San Antonio, Texas, 78229
TriWest Research Associates
San Diego, California, 92108
Precision Comprehensive Clinical Research Solutions
San Leandro, California, 94578-2630
Inspire Santa Fe Medical Group
Santa Fe, New Mexico, 87505
Saint John's Health Center - Providence St John's Health Ctr
Santa Monica, California, 90404
Shelby Clinical Research - Family Medicine
Shelby, North Carolina, 28152
Arthritis Northwest, PLLC - Research
Spokane, Washington, 99204
Texas Research Center
Sugar Land, Texas, 77479
Low Country Rheumatology
Summerville, South Carolina, 29486-7887
Arizona Arthritis & Rheumatology Research, PLLC
Sun City, Arizona, 85351
D&H Tamarac Research Center
Tamarac, Florida, 33321
GCP Clinical Research
Tampa, Florida, 33609
ClinPro Research Solutions, LLC
Tampa, Florida, 33613
C.V. Mehta MD Medical Corporation
Temecula, California, 92592
Arizona Arthritis and Rheumatology
Tucson, Arizona, 85704
Foothill Arthritis
Tujunga, California, 91042
Velocity Clinical Research-Vestal
Vestal, New York, 13850
Velocity Clinical Research - Salt Lake City (West Jordan)
West Jordan, Utah, 84088
Medvin Clinical Research
Whittier, California, 90602
About this study
Official title: A Phase 4, Randomized, Double-blind, Multicenter Non-inferiority Trial Evaluating the Efficacy and Safety of Intravenous KRYSTEXXA® (Pegloticase) Administered Every 4 Weeks Compared With KRYSTEXXA Administered Every 2 Weeks With Co-administration of Weekly Doses of Methotrexate, Followed by an Open-label Extension, in Participants With Uncontrolled Refractory Gout (FORWARD II)
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.
Read the detailed description
Acquired from Horizon in 2024.
- Conditions
- Gout
- Being tested
- Pegloticase, Methotrexate
- Keywords
- Uncontrolled Gout, pegloticase, Krystexxa, Methotrexate, Chronic Gout
- Medical subject headings
- Gout
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PegloticaseBiological
Also called Krystexxa
IV infusion
MethotrexateDrug
Oral
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: Pegloticase; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6
Responders were defined as participants who achieved and maintained sUA levels below 6 mg/dL for at least 80% of the time during Month 6. Responders who met sUA discontinuation criteria (2 consecutive sUA > 6 mg/dL), regardless of treatment status were considered non-responders.
Measured: Month 6 (Weeks 20, 21, 22, 23, and 24)
Secondary outcomes (1)
Percentage of Participants With Complete Resolution of ≥ 1 Tophus at Week 24 in Participants With Tophi at Baseline
Measured: Baseline, Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2024
- Study start18 Mar 2024
- Primary completion30 Jul 2025
- Study completion26 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GoutStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 306 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06229145
- Sponsor's protocol ID
- HZNP-KRY-409
- Status last verified
- Sep 2026
- First submitted
- 19 Jan 2024
- Last updated
- 17 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.