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Study of Pegloticase (KRYSTEXXA®) Plus Methotrexate in Patients With Uncontrolled Gout (MIRROR OL)

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ClinicalTrials.gov Identifier: NCT03635957
Recruitment Status : Active, not recruiting
First Posted : August 17, 2018
Last Update Posted : June 4, 2019
Sponsor:
Information provided by (Responsible Party):
Horizon Pharma Rheumatology LLC

Brief Summary:

This is a multicenter study of pegloticase (KRYSTEXXA®) given with methotrexate (MTX) in adult participants with uncontrolled gout. Approximately 12 to 17 participants will be enrolled. Study duration will be approximately 82 weeks.

The purpose of this study is to assess the efficacy, safety, tolerability, and blood levels of pegloticase when given with concomitant MTX administered to prevent immunogenicity against pegloticase, in adults with uncontrolled gout.


Condition or disease Intervention/treatment Phase
Gout Biological: Pegloticase with MTX Phase 4

Detailed Description:

This is a multicenter study of pegloticase (KRYSTEXXA®) plus methotrexate (MTX) in adult participants with uncontrolled gout.

The study design will include: 1) up to a 2-week Screening Period (screening should be complete within 2 weeks prior to Week -4), 2) a 4-week MTX Run in Period (Week - 4 through Day 1); 3) a 52-week Pegloticase + IMM (immunomodulator), (Pegloticase + MTX) Period 4) a Safety Follow-up (Phone/Email/Site Visit) and 5) a 3 and 6 month Post Treatment Follow-up.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled GOut Receiving KRYSTEXXA® (Pegloticase) (MIRROR Open-Label [OL])
Actual Study Start Date : September 26, 2018
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Gout
MedlinePlus related topics: Gout

Arm Intervention/treatment
Experimental: Pegloticase with methotrexate (MTX) (single arm)
Participants will receive MTX during the run-in period and then pegloticase with MTX for 52 weeks
Biological: Pegloticase with MTX
Participants will receive MTX during the run-in period and then pegloticase with MTX for 52 weeks
Other Name: methotrexate (MTX)




Primary Outcome Measures :
  1. Proportion of Serum Uric Acid Responders (sUA < 6 mg/dL) during Month 6 [ Time Frame: Month 6 ]
    Serum uric acid (sUA) responders are defined as participants achieving and maintaining sUA < 6 mg/dL for at least 80 % of the time during Month 6 (Weeks 20, 22, and 24).


Secondary Outcome Measures :
  1. Proportion of Serum Uric Acid Responders (sUA < 6 mg/dL) during Month 3 [ Time Frame: Month 3 ]
    Serum uric acid (sUA) responders are defined as participants achieving and maintaining sUA < 6 mg/dL for at least 80% of the time during Month 3 (Weeks 10, 12, and 14).

  2. Proportion of Overall Serum Uric Acid Responders (sUA < 6 mg/dL) [ Time Frame: Month 3 and Month 6 combined ]
    Serum uric acid (sUA) overall responders are defined as participants achieving and maintaining sUA < 6 mg/dL for at least 80% of the time during Month 3 and Month 6 combined, (Weeks 10,12,14, 20, 22, and 24).

  3. Proportion of Serum Uric Acid Responders (sUA 5 mg/dL) during Month 3 [ Time Frame: Month 3 ]
    Serum uric acid (sUA) responders are defined as participants achieving and maintaining sUA < 5 mg/dL for at least 80% of the time during Month 3.

  4. Proportion of Serum Uric Acid Responders (sUA 5 mg/dL) during Month 6 [ Time Frame: Month 6 ]
    Serum uric acid (sUA) responders are defined as participants achieving and maintaining sUA < 5 mg/dL for at least 80% of the time during Month 6.

  5. Proportion of Overall Serum Uric Acid Responders (sUA < 5 mg/dL) [ Time Frame: Month 3 and Month 6 combined ]
    Serum uric acid (sUA) overall responders are defined as participants achieving and maintaining sUA < 5 mg/dL for at least 80% of the time during Month 3 and Month 6 combined.

  6. Mean change in serum uric acid from baseline to Weeks 14, 24, 36, 52 [ Time Frame: Baseline, Weeks 14, 24, 36, 52 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 study.
  3. Adult men or women ≥18 to ≤65 years of age.
  4. 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 the Screening/(methotrexate) MTX Run in Period; participants must agree to use 2 reliable forms of contraception during the study, 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 dosing) and continue for 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.
  5. Men who are not vasectomized must not impregnant their female partner during the study and for at least 3 months after the last dose of MTX.
  6. Hyperuricemia at the Screening, Week -4, or Week -2 Visit of the Screening/MTX Run in Period, as documented by sUA ≥6 mg/dL.
  7. Uncontrolled gout, defined as meeting the following criteria:

    sUA ≥6 mg/dL prior to entry into the pegloticase +IMM Period (any laboratory tests during screening up to and including during the MTX Run in Period) and at least 1 of the following: inability to maintain sUA <6 mg/dL on other urate-lowering therapy. intolerable side effects associated with current urate-lowering therapy; functionally limiting tophaceous deposits (including those detected clinically or by DECT imaging)

  8. Able to tolerate MTX 15 mg for 4 weeks during the Screening/MTX Run-in Period prior to the first dose of pegloticase.

Exclusion Criteria:

  1. Weight >160 kg (352 pounds).
  2. Any serious acute bacterial infection, unless treated and completely resolved with antibiotics at least 2 weeks prior to the Week -4 Visit of the Screening/MTX Run-in Period.
  3. Severe chronic or recurrent bacterial infections, such as recurrent pneumonia or chronic bronchiectasis.
  4. Current immunocompromised condition, including current or chronic treatment with systemic immunosuppressive agents, including prednisone >10 mg/day or equivalent dose of other corticosteroid.
  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.
  8. Human immunodeficiency virus (HIV) positivity (tested at the Screening Visit).
  9. Glucose-6-phosphate dehydrogenase (G6PD) deficiency (tested at the Screening Visit).
  10. Severe chronic renal impairment (glomerular filtration rate <25 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) at the end of the Screening/MTX Run-in Period.
  12. Pregnant, planning to become pregnant, breastfeeding, planning to impregnant female partner, or not on an effective form of birth control, as determined by the Investigator.
  13. Prior treatment with pegloticase (KRYSTEXXA®), 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 study.
  18. Current liver disease, as determined by alanine transaminase or aspartate transaminase levels >3 times upper limit of normal at the Screening Visit.
  19. Currently receiving systemic or radiologic treatment for ongoing cancer, excluding non melanoma skin cancer.
  20. History of malignancy within 5 years other than non-melanoma skin cancer or in situ carcinoma of cervix.
  21. Uncontrolled hyperglycemia with a plasma glucose value >240 mg/dL at screening that is not subsequently controlled by the end of the Screening/MTX Run-in Period.
  22. Diagnosis of osteomyelitis.
  23. Known history of hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome.
  24. Unsuitable candidate for the study, based on the opinion of the Investigator (e.g., cognitive impairment), such that participation might create undue risk to the participant or interfere with the participant's ability to comply with the protocol requirements or complete the study.
  25. Alcohol use in excess of 3 alcoholic beverages per week.
  26. Currently receiving allopurinol and unable to discontinue medication 7 days prior to MTX dosing at Week -4 and unable to discontinue treatment during the duration of the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03635957


Locations
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United States, Alaska
Orthopedic Physicians Alaska
Anchorage, Alaska, United States, 99508
United States, Arizona
Arizona Arthritis & Rheumatology -West Valley
Glendale, Arizona, United States, 85306
Arizona Arthritis & Rheumatology -East Valley
Mesa, Arizona, United States, 85210
United States, Florida
Avail Clinical Research
DeLand, Florida, United States, 32720
United States, Washington
Western Washington Arthritis Clinic
Bothell, Washington, United States, 98021
Arthritis Northwest PLLC
Spokane, Washington, United States, 99204
Sponsors and Collaborators
Horizon Pharma Rheumatology LLC
Investigators
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Study Director: Colleen Canavan, BS Horizon Pharma Rheumatology LLC

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Responsible Party: Horizon Pharma Rheumatology LLC
ClinicalTrials.gov Identifier: NCT03635957     History of Changes
Other Study ID Numbers: HZNP-KRY-201
First Posted: August 17, 2018    Key Record Dates
Last Update Posted: June 4, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Horizon Pharma Rheumatology LLC:
gout
uncontrolled gout

Additional relevant MeSH terms:
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Gout
Arthritis
Joint Diseases
Musculoskeletal Diseases
Crystal Arthropathies
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors