A Phase 4, Open-label Study of KRYSTEXXA® (Pegloticase) Co-administered With Methotrexate (MTX) in Patients With Uncontrolled Gout (FORWARD OL)

NCT04762498 | Completed Phase 4 FDA Drug

• 1 other identifier: HZNP-KRY-408
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 12

Brief Summary

This trial is to assess efficacy, safety, blood levels and bodily effects of up to 2 dose levels of intravenous (IV) pegloticase (KRYSTEXXA) infusions at every 4 week intervals (Q4 Weeks) for up to 6 months (Day 1 to 24 weeks with an optional 24 - 48 weeks treatment duration) when given in combination with weekly oral doses of methotrexate (MTX). The goal is to identify an appropriate dose to be administered every 4 weeks to be used for future clinical trials for patients with chronic gout that does not adequately respond to conventional therapy.

Conditions

Uncontrolled Gout; Chronic Gout

Keywords

Gout; KRYSTEXXA; Pegloticase; Methotrexate; Uncontrolled gout

Outcome Measures

Primary Outcomes (2)

• Proportion of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6

  Responders are defined as participants achieving and maintaining sUA \< 6 mg/dL for at least 80% of the time during Month 6. Participants meeting the sUA discontinuation criteria (pre-infusion sUA \>6 mg/dL at 2 consecutive scheduled trial visits beginning with the Week 1 Visit) were counted as non-responders.

  Month 6 (Weeks 20, 21, 22, 23, and 24)

• Time to first sUA ≥6 mg/dL after first achieving sUA <6 mg/dL, from the first pegloticase infusion until Week 24

  Day 1 to Week 24

Secondary Outcomes (5)

• Pharmacokinetic parameters (e.g., AUC and, Cmax)

  Baseline to Week 48

• Proportion of subjects with pre-infusion sUA <6 mg/dL at each scheduled visit

  Baseline to Week 48

• Area under the sUA concentration vs time curve from Day 1 to Week 24 and Day 1 to Week 48

  Day 1 to Week 24 and Day 1 to Week 48

• Proportion of the subjects sustained sUA< 6 mg/dL from Day 1 to Week 24 and Day 1 to Week 48

  Day 1 to Week 24 and Day 1 to Week 48

• Proportion of subjects with anti-uricase antibodies and the proportion of subjects with anti-poly (ethylene glycol) antibodies and their titers at each scheduled visit

  Baseline to Week 48

Study Arms (2)

Pegloticase 16mg cohort

EXPERIMENTAL

16 mg IV dose of pegloticase q4 weeks with 15 mg methotrexate (MTX) weekly

Biological: Pegloticase; Drug: Methotrexate (MTX)

Pegloticase 24/32mg cohort

EXPERIMENTAL

24 to 32 mg IV dose of pegloticase q4 weeks with 15 mg MTX weekly

Biological: Pegloticase; Drug: Methotrexate (MTX)

Interventions

Pegloticase BIOLOGICAL

IV dose of pegloticase q4 weeks co-administered with weekly oral methotrexate

Pegloticase 16mg cohort; Pegloticase 24/32mg cohort

Methotrexate (MTX) DRUG

15 mg oral dose methotrexate administered weekly

Pegloticase 16mg cohort; Pegloticase 24/32mg cohort

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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 trial.
• Adult men or women ≥18 and \<80 years of age.
• Uncontrolled gout, defined as meeting the following criteria:
• Hyperuricemia during the screening period defined as sUA ≥6 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 as evidenced by either clinical signs consistent with chronic synovitis on clinical examination or the presence of typical gouty erosion(s) on hand and/or foot X-rays
• Willing to discontinue any oral urate lowering therapy for at least 7 days prior to MTX dosing at Week -4 and remain off while receiving pegloticase treatments.
• 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 -4; subjects must agree to use 2 reliable forms of contraception during the trial, 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) and continue for 4 weeks/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.
• 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, beginning with the initiation of MTX at Week -4 and continuing and for at least 3 months after the last dose of MTX.
• Able to tolerate MTX 15 mg orally for 4 weeks (Week -4 through Day 1) prior to enrollment.

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 Day 1 Visit.
• Severe chronic or recurrent bacterial infections, such as recurrent pneumonia or chronic bronchiectasis.
• 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.
• Glucose-6-phosphate dehydrogenase deficiency (tested at the Screening Visit centrally or locally).
• 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 enrollment at Day 1.
• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (12)

Orthopedic Physicians Alaska

Anchorage, Alaska, 99508, United States

Location

Arizona Arthritis & Rheumatology Research, PLLC

Glendale, Arizona, 85306, United States

Location

East Bay Rheumatology Medical Group, Inc.

San Leandro, California, 94578, United States

Location

ProHealth Research Center

Doral, Florida, 33166, United States

Location

Napa Research Center

Pompano Beach, Florida, 33064, United States

Location

GCP Clinical Research

Tampa, Florida, 33064, United States

Location

The Center for Rheumatology and Bone Research

Wheaton, Maryland, 20902, United States

Location

Shelby Clinical Research, LLC

Shelby, North Carolina, 28150, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Biopharma Informatic, LLC

Houston, Texas, 77043, United States

Location

Arthritis Clinic: Western Washington Medical Group

Bothell, Washington, 98021, United States

Location

Arthritis Northwest PLLC

Spokane, Washington, 99204, United States

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Gout

Interventions

Pegloticase; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

• Supra Verma, MD

  Horizon Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Screening period up to 35 days, followed by 4-week methotrexate (MTX) tolerability run-in. Treatment consists of pegloticase IV Q4 Wks dose for a total of 6 infusions (24 Weeks) with co-administered weekly oral MTX. Optional extension treatment (24-48 weeks) will be available for 6 more infusions (total of 12). Study will consist of Cohort 1: 16 mg pegloticase, co-administered with weekly doses of oral MTX; and, potential Cohort 2: 24 to 32 mg pegloticase, co-administered with weekly doses of oral MTX and/or potential infusion duration reduction to 60 min.

Study Record Dates

• First Submitted: February 12, 2021
• First Posted: February 21, 2021
• Study Start: January 26, 2021
• Primary Completion: May 18, 2023
• Study Completion: December 20, 2023
• Last Updated: October 1, 2025

Record last verified: 2025-09

Locations

US (12)