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

April 24, 2024 updated by: Horizon Therapeutics Ireland DAC

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

240

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Alaska
      • Anchorage, Alaska, United States, 99508
        • Recruiting
        • Orthopedic Physicians Alaska
        • Contact:
        • Principal Investigator:
          • John Botson
    • Arizona
      • Chandler, Arizona, United States, 85225
        • Recruiting
        • Arizona Arthritis and Rheumatology Research - Chandler
        • Principal Investigator:
          • Amer Al-Khoudari
      • Flagstaff, Arizona, United States, 86001
        • Recruiting
        • Arizona Arthritis and Rheumatology Research PLCC-Flagstaff
        • Principal Investigator:
          • Alexander Hu
      • Gilbert, Arizona, United States, 85297
        • Recruiting
        • Arizona Arthritis and Rheumatology Research - Gilbert
        • Principal Investigator:
          • JoonHee Lim
      • Mesa, Arizona, United States, 85210
        • Recruiting
        • Arizona Arthritis and Rheumatology Research - Mesa
        • Principal Investigator:
          • Nikila Kumar
      • Phoenix, Arizona, United States, 85037
        • Recruiting
        • Arizona Arthritis and Rheumatology Research- Phoenix
        • Principal Investigator:
          • Andrew Sharobeem
    • California
      • Covina, California, United States, 91722
        • Recruiting
        • Medvin Clinical Research-Covina
        • Principal Investigator:
          • Samy Metyas
        • Contact:
      • Riverside, California, United States, 92518
        • Recruiting
        • Medvin Clinical Research - Cactus Avenue
        • Contact:
        • Principal Investigator:
          • Amal Mehta
      • San Diego, California, United States, 92108
        • Recruiting
        • TriWest Research Associates - San Diego
        • Principal Investigator:
          • Arthur Mabaquiao
        • Contact:
      • San Leandro, California, United States, 94578
        • Recruiting
        • Precision Comprehensive Clinical Research Solutions
        • Principal Investigator:
          • Suneet Grewal
      • Tujunga, California, United States, 91042
        • Recruiting
        • Medvin Clinical Research- Tujunga
        • Principal Investigator:
          • Dan La
        • Contact:
    • Florida
      • Aventura, Florida, United States, 33180
        • Recruiting
        • Arthritis and Rheumatic Disease Specialties
        • Principal Investigator:
          • Norman Gaylis
      • Doral, Florida, United States, 33166
      • Hialeah, Florida, United States, 33016
        • Recruiting
        • New Generation of Medical Research
        • Principal Investigator:
          • Karelia Ruiz
      • Margate, Florida, United States, 33063
        • Recruiting
        • Life Clinical Trials
        • Principal Investigator:
          • Jigar Shah
      • Miami, Florida, United States, 33155
        • Recruiting
        • D and H National Research Centers
        • Principal Investigator:
          • Jorge Amaya
        • Contact:
      • Tamarac, Florida, United States, 33321
        • Recruiting
        • D and H Tamarac Reseach Center
        • Principal Investigator:
          • Mazyar Rouhani
        • Contact:
      • Tampa, Florida, United States, 33609
        • Recruiting
        • GCP Clinical Research
        • Principal Investigator:
          • Karon Locicero
      • Tampa, Florida, United States, 33609
        • Recruiting
        • ClinPro Research Solutions
        • Principal Investigator:
          • Thomas Taylor
      • Winter Park, Florida, United States, 32789
    • Georgia
      • Newnan, Georgia, United States, 30265
        • Recruiting
        • Vista Clinical Research
        • Principal Investigator:
          • Sandeep Vaid
        • Contact:
    • Idaho
      • Meridian, Idaho, United States, 23642
        • Recruiting
        • Velocity Clinical Research Boise
        • Principal Investigator:
          • Mark Turner
    • Illinois
      • Chicago, Illinois, United States, 60640
        • Recruiting
        • Great Lakes Clinical Trials
        • Principal Investigator:
          • Manish Jain
        • Contact:
      • Gurnee, Illinois, United States, 60031
        • Recruiting
        • Great Lakes Clinical Trials - Brookside Drive
        • Principal Investigator:
          • Yevgeniy Bukhman
    • Michigan
      • Lansing, Michigan, United States, 48911
        • Recruiting
        • June DO PC
        • Principal Investigator:
          • Joshua June
    • New Mexico
      • Santa Fe, New Mexico, United States, 87505
        • Recruiting
        • Inspire Santa Fe Medical Group
        • Principal Investigator:
          • Hillary Norton
    • North Carolina
      • Denver, North Carolina, United States, 28037
        • Recruiting
        • Research Carolina Elite
        • Principal Investigator:
          • Donald Horner
        • Contact:
      • Greensboro, North Carolina, United States, 27410
        • Recruiting
        • Triad Clinical Trials
        • Principal Investigator:
          • Richard Montgomery
      • Shelby, North Carolina, United States, 28150
        • Recruiting
        • Shelby Clinical Research
        • Contact:
        • Principal Investigator:
          • Christian Martin
    • Ohio
      • Beachwood, Ohio, United States, 44122
        • Recruiting
        • Velocity Clinical Research Cleveland Ohio
        • Principal Investigator:
          • Margaret Rhee
      • Cincinnati, Ohio, United States, 45242
        • Recruiting
        • Velocity Clinical Research
        • Principal Investigator:
          • Seref Bornovali
    • Pennsylvania
      • Duncansville, Pennsylvania, United States, 16635
        • Recruiting
        • Altoona Center for Clinical Research
        • Contact:
        • Principal Investigator:
          • Alan Kivitz
    • South Carolina
      • Rock Hill, South Carolina, United States, 29730
        • Recruiting
        • Premier Clinics PA
        • Principal Investigator:
          • Bamidele Ekunsanmi
      • Summerville, South Carolina, United States, 29486
        • Recruiting
        • Articularis Healthcare Group dba Low Country Rheumatology
        • Principal Investigator:
          • Nicholas Holdgate
        • Contact:
    • Texas
      • Amarillo, Texas, United States, 79124
        • Recruiting
        • Amarillo Center for Clinical Research - Clinedge - PPDS
        • Principal Investigator:
          • Constantine Saadeh
      • Houston, Texas, United States, 77099
        • Recruiting
        • Pioneer Research Solutions
        • Contact:
        • Principal Investigator:
          • Francisco Velazquez
      • Houston, Texas, United States, 77074
        • Recruiting
        • Clinical Trials Network
        • Principal Investigator:
          • Maxwell Axler
      • Houston, Texas, United States, 77061
        • Recruiting
        • Synergy Groups Medical
        • Principal Investigator:
          • Caroline Mbogua
      • Plano, Texas, United States, 75093
        • Recruiting
        • AIM Trials
        • Principal Investigator:
          • Saumil Mehta
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • Clinical Trials of Texas -Flourish Research
        • Contact:
        • Principal Investigator:
          • Pendleton Wickersham
    • Utah
      • West Jordan, Utah, United States, 84088
        • Recruiting
        • Velocity Clinical Research - West Jordan
        • Principal Investigator:
          • Barbara Rizzardi
    • Virginia
      • Portsmouth, Virginia, United States, 23703
        • Recruiting
        • Velocity Clinical Research - Portsmouth
        • Principal Investigator:
          • Banu Myneni
    • Washington
      • Spokane, Washington, United States, 99204
        • Recruiting
        • Arthritis Northwest PLLC
        • Contact:
        • Principal Investigator:
          • Eric Mueller

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pegloticase + Methotrexate Q4W
16 mg pegloticase will be administered intravenously every 4 weeks for 24 weeks during double blind treatment and 24 weeks during open label.
Drug: Methotrexate
Oral
Biological: Pegloticase
IV infusion
Experimental: Pegloticase + Methotrexate Q2W
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.
Drug: Methotrexate
Oral
Biological: Pegloticase
IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proportion of Participants achieving and maintaining serum uric acid (sUA) < 6 mg/dL at least 80% of the time
Time Frame: Month 6
Month 6

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportion of Participants with complete resolution of ≥ 1 tophus
Time Frame: Week 24
Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Horizon Therapeutics Ireland DAC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 22, 2024

Primary Completion (Estimated)

September 1, 2025

Study Completion (Estimated)

May 1, 2026

Study Registration Dates

First Submitted

January 19, 2024

First Submitted That Met QC Criteria

January 19, 2024

First Posted (Actual)

January 29, 2024

Study Record Updates

Last Update Posted (Actual)

April 25, 2024

Last Update Submitted That Met QC Criteria

April 24, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HZNP-KRY-409

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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