Clinical trial NCT06229145: 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
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Gout
Keywords: Uncontrolled Gout
pegloticase
Krystexxa
Methotrexate
Chronic Gout
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2024-01-29
Enrollment: 262
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Adult men or women ≥ 18 years of age
2. 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
3. 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
4. Women of childbearing potential must have negative serum/urine pregnancy tests during screening and Week -4.
5. 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.

Exclusion Criteria:

1. Severe chronic or recurrent bacterial infections, such as recurrent pneumonia or chronic bronchiectasis
2. 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)
3. History of any transplant surgery requiring maintenance immunosuppressive therapy
4. Known history of hepatitis B virus surface antigen positivity or hepatitis B DNA positivity
5. Known history of hepatitis C virus RNA positivity, unless treated and viral load is negative
6. Known history of human immunodeficiency virus (HIV) positivity
7. G6PD deficiency (quantitative test at the Screening Visit centrally or locally)
8. 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
9. 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
10. Prior treatment with pegloticase, another recombinant uricase (rasburicase) or concomitant therapy with a PEG-conjugated drug
11. Unable to tolerate MTX 15 mg orally during the MTX Run-in Period
12. Chronic liver disease
13. White blood cell count \< 4,000/μL, hematocrit \< 32% or platelet count \< 75,000/μL
14. Currently receiving systemic or radiologic treatment for ongoing cancer
15. History of malignancy within 5 years other than non-melanoma skin cancer or in situ carcinoma of cervix
16. Diagnosis of osteomyelitis
17. Known history of hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome
18. 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)
19. Current pulmonary fibrosis, bronchiectasis or interstitial pneumonitis. If deemed necessary by the Investigator, a chest X-ray may be performed during Screening.

Primary outcomes:
measure: Proportion of Participants achieving and maintaining serum uric acid (sUA) < 6 mg/dL at least 80% of the time
timeFrame: Month 6
Secondary outcomes:
measure: Proportion of Participants with complete resolution of ≥ 1 tophus
timeFrame: Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham (UAB)
state: Alabama
city: Anchorage
country: United States
facility: Orthopedic Physicians Alaska - Rheumatology and Infusion
state: Alaska
city: Chandler
country: United States
facility: Arizona Arthritis and Rheumatology
state: Arizona
city: Flagstaff
country: United States
facility: Arizona Arthritis and Rheumatology Rese
state: Arizona
city: Gilbert
country: United States
facility: Arizona Arthritis & Rheumatology
state: Arizona
city: Mesa
country: United States
facility: Arizona ArthritisRheumatology Resea
state: Arizona
city: Phoenix
country: United States
facility: Arizona Arthritis & Rheumatology
state: Arizona
city: Phoenix
country: United States
facility: Arizona Arthritis & Rheumatology
state: Arizona
city: Phoenix
country: United States
facility: Arizona Arthritis and Rheumatology Research
state: Arizona
city: Sun City
country: United States
facility: Arizona Arthritis & Rheumatology
state: Arizona
city: Tucson
country: United States
facility: Arizona Arthritis and Rheumatology
state: Arizona
city: Covina
country: United States
facility: Covina Arthritis Clinic
state: California
city: Hemet
country: United States
facility: Medvin Clinical Research- Riverside
state: California
city: San Diego
country: United States
facility: TriWest Research Associates
state: California
city: San Leandro
country: United States
facility: PCCRS
state: California
city: Santa Monica
country: United States
facility: Saint John's Health Center
state: California
city: Temecula
country: United States
facility: C.V. Mehta MD Medical Corporation
state: California
city: Tujunga
country: United States
facility: Foothill Arthritis
state: California
city: Whittier
country: United States
facility: Medvin Clinical Research
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Colorado Springs
country: United States
facility: Lynn Institute of the Rockies
state: Colorado
city: Denver
country: United States
facility: Denver Arthritis Clinic
state: Colorado
city: Aventura
country: United States
facility: Arthritis & Rheumatic Disease
state: Florida
city: Doral
country: United States
facility: Prohealth Research Center
state: Florida
city: Homestead
country: United States
facility: Homestead Associates in Research,Inc
state: Florida
city: Margate
country: United States
facility: Life Clinical Trials
state: Florida
city: Miami
country: United States
facility: D&H National Research Centers, Inc.
state: Florida
city: Miami
country: United States
facility: Well Pharma
state: Florida
city: Miami
country: United States
facility: Felicidad Medical Research, LLC.
state: Florida
city: Naples
country: United States
facility: New Generation Of Medical Research
state: Florida
city: Plantation
country: United States
facility: IRIS Research & Development
state: Florida
city: Pompano Beach
country: United States
facility: D&H Pompano Research Center
state: Florida
city: Tamarac
country: United States
facility: D&H Tamarac Research Center
state: Florida
city: Tampa
country: United States
facility: ClinPro Research Solutions, LLC
state: Florida
city: Tampa
country: United States
facility: GCP Clinical Research
state: Florida
city: Winter Park
country: United States
facility: Conquest Research
state: Florida
city: Gainesville
country: United States
facility: Arthritis Center of North Georgia
state: Georgia
city: Newnan
country: United States
facility: Vista Clinical Research, LLC
state: Georgia
city: Meridian
country: United States
facility: Velocity Clinical Research - Boise
state: Idaho
city: Chicago
country: United States
facility: Great Lakes Clin. Trials
state: Illinois
city: Gurnee
country: United States
facility: Great Lakes Clinical Trials - Gurnee
state: Illinois
city: Hinsdale
country: United States
facility: Crowley CORE
state: Illinois
city: New Albany
country: United States
facility: Lake Cumberland Rheumatology, PLLC
state: Indiana
city: Louisville
country: United States
facility: L-MARC Research Center
state: Kentucky
city: New Orleans
country: United States
facility: Velocity CR - New Orleans
state: Louisiana
city: Ann Arbor
country: United States
facility: Michigan Medicine
state: Michigan
city: Lansing
country: United States
facility: June DO, PC
state: Michigan
city: Saint Clair Shores
country: United States
facility: Clinical Research Institute of Michigan, LLC
state: Michigan
city: Santa Fe
country: United States
facility: Inspire Santa Fe Medical Group
state: New Mexico
city: Vestal
country: United States
facility: Velocity Clinical Research-Vestal
state: New York
city: Charlotte
country: United States
facility: OnSite Clinical Solutions, LLC
state: North Carolina
city: Denver
country: United States
facility: Research Carolina Elite, LLC
state: North Carolina
city: Greensboro
country: United States
facility: Triad Clinical Trials
state: North Carolina
city: Hickory
country: United States
facility: Accellacare of Hickory
state: North Carolina
city: Leland
country: United States
facility: Cape Fear Arthritis Care
state: North Carolina
city: Shelby
country: United States
facility: Shelby Clinical Research
state: North Carolina
city: Beachwood
country: United States
facility: Velocity Clinical Res, Cleveland
state: Ohio
city: Cincinnati
country: United States
facility: Velocity Clinical Research - Cincinnati
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research - Research
state: Pennsylvania
city: Greenville
country: United States
facility: Velocity Clinical Research, Greenville
state: South Carolina
city: Rock Hill
country: United States
facility: Premier Clinics Pa
state: South Carolina
city: Summerville
country: United States
facility: Low Country Rheumatology
state: South Carolina
city: Amarillo
country: United States
facility: Amarillo Center for Clinical Research, Ltd.
state: Texas
city: Houston
country: United States
facility: Synergy Groups Medical LLC
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions, Inc.
state: Texas
city: Plano
country: United States
facility: AIM Trials - Internal Medicine
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: Sugar Land
country: United States
facility: Siena Research Network
state: Texas
city: West Jordan
country: United States
facility: Velocity Clinical Research - Salt Lake City
state: Utah
city: Suffolk
country: United States
facility: Velocity Clin Research-Portsmouth
state: Virginia
city: Spokane
country: United States
facility: Arthritis Northwest, PLLC - Research
state: Washington
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: