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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 80 Years
Gender All
More Inclusion & Exclusion 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. 4. 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) would also meet exclusion criteria. 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04762498
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 4
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Horizon Therapeutics Ireland DAC
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Jeff White, BA
Principal Investigator Affiliation Horizon Therapeutics
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Uncontrolled Gout, Chronic Gout
Additional Details

The primary objective is to choose a dose for further investigation by assessing the effect of pegloticase 16 mg dose with a possibility of potential additional dose (e.g., 24 or 32 mg) administered via IV Q4 Wks, 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.

Arms & Interventions

Arms

Experimental: Pegloticase 16mg cohort

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

Experimental: Pegloticase 24/32mg cohort

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

Interventions

Biological: - Pegloticase and Methotrexate (MTX)

16 mg IV dose of pegloticase q4 weeks [with a potential for higher dose in cohort 2 (24 or 32 mg)], co-administered with 15 mg oral dose methotrexate weekly

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

ProHealth Research Center, Doral, Florida

Status

Recruiting

Address

ProHealth Research Center

Doral, Florida, 33166

Site Contact

Johanna Garcia

[email protected]

305-960-7934