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

NCT ID: NCT04762498

Last Updated: 2025-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-26
• Study Completion Date: 2023-12-20

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.

Detailed Description

The primary objective is to choose a dose for further investigation by assessing the effect of up to 2 dose levels of pegloticase administered IV Q4 weeks, co-administered with weekly doses of oral MTX, as measured by the sustained normalization of serum uric acid (sUA) to < 6 mg/dL for at least 80% of the time during Month 6 and the duration of sUA to < 6 mg/dL over 24 week treatment period in adult participants with chronic gout refractory to conventional therapy.

Acquired from Horizon in 2024.

Conditions

Uncontrolled Gout; Chronic Gout

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pegloticase 16mg cohort

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

Group Type: EXPERIMENTAL

Pegloticase

Intervention Type: BIOLOGICAL

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

Methotrexate (MTX)

Intervention Type: DRUG

15 mg oral dose methotrexate administered weekly

Pegloticase 24/32mg cohort

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

Group Type: EXPERIMENTAL

Pegloticase

Intervention Type: BIOLOGICAL

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

Methotrexate (MTX)

Intervention Type: DRUG

15 mg oral dose methotrexate administered weekly

Interventions

Pegloticase

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

Intervention Type: BIOLOGICAL

Methotrexate (MTX)

15 mg oral dose methotrexate administered weekly

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Willing and able to give informed consent.

2. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.

3. Adult men or women ≥18 and <80 years of age.

4. 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

5. 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.

6. 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.

7. 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.

8. Able to tolerate MTX 15 mg orally for 4 weeks (Week -4 through Day 1) prior to enrollment.

Exclusion Criteria

1. Weight >160 kg (352 pounds) at Screening.

2. Any serious acute bacterial infection, unless treated and completely resolved with antibiotics at least 2 weeks prior to the Day 1 Visit.

3. Severe chronic or recurrent bacterial infections, such as recurrent pneumonia or chronic bronchiectasis.

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, unless treated and viral load is negative.

8. Known history of Human Immunodeficiency Virus (HIV) positivity.

9. Glucose-6-phosphate dehydrogenase deficiency (tested at the Screening Visit centrally or locally).

10. Chronic renal impairment defined as estimated glomerular filtration rate (eGFR) <40 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) prior to enrollment at Day 1.

12. 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.

13. Prior treatment with pegloticase, 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 trial.

18. Liver transaminase levels (AST or ALT) > 1.25 X upper limit of normal (ULN) or albumin < the lower limit of normal (LLN) at the Screening Visit.

19. Chronic liver disease.

20. White blood cell count <4000/µl, hematocrit <32 percent, or platelet count <75,000/µl.

21. Currently receiving systemic or radiologic treatment for ongoing cancer, excluding non-melanoma skin cancer.

22. History of malignancy within 5 years other than non-melanoma skin cancer or in situ carcinoma of cervix.

23. Diagnosis of osteomyelitis.

24. Known history of hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome.

25. Unsuitable candidate for the trial, based on the opinion of the Investigator (e.g., cognitive impairment), such that participation might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements or complete the trial.

26. Alcohol use in excess of 3 alcoholic beverages per week.

27. A known intolerance to all protocol standard gout flare prophylaxis regimens (i.e., subject must be able to tolerate at least one: colchicine and/or non-steroidal anti-inflammatory drugs and/or low dose prednisone ≤10 mg/day).

28. Current pulmonary fibrosis, bronchiectasis or interstitial pneumonitis. If deemed necessary by the Investigator, a chest X-ray may be performed during Screening.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Supra Verma, MD

Role: STUDY_DIRECTOR

Horizon Therapeutics

Locations

Orthopedic Physicians Alaska

Anchorage, Alaska, United States

Arizona Arthritis & Rheumatology Research, PLLC

Glendale, Arizona, United States

East Bay Rheumatology Medical Group, Inc.

San Leandro, California, United States

ProHealth Research Center

Doral, Florida, United States

Napa Research Center

Pompano Beach, Florida, United States

GCP Clinical Research

Tampa, Florida, United States

The Center for Rheumatology and Bone Research

Wheaton, Maryland, United States

Shelby Clinical Research, LLC

Shelby, North Carolina, United States

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

Biopharma Informatic, LLC

Houston, Texas, United States

Arthritis Clinic: Western Washington Medical Group

Bothell, Washington, United States

Arthritis Northwest PLLC

Spokane, Washington, United States

Countries

United States

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

HZNP-KRY-408

Identifier Type: -

Identifier Source: org_study_id