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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03635957
Recruitment Status : Active, not recruiting
First Posted : August 17, 2018
Last Update Posted : February 11, 2020
Sponsor:
Information provided by (Responsible Party):
Horizon Pharma Ireland, Ltd., Dublin Ireland ( Horizon Therapeutics Ireland DAC )

Tracking Information
First Submitted Date  ICMJE August 9, 2018
First Posted Date  ICMJE August 17, 2018
Last Update Posted Date February 11, 2020
Actual Study Start Date  ICMJE September 26, 2018
Actual Primary Completion Date October 23, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2019)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: August 15, 2018)
Proportion of Serum Uric Acid Responders (sUA < 6 mg/dL) at 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) and with at least one sUA level < 5 mg/dL between the time after the first KRYSTEXXA® infusion to Week 14, inclusive. Participants who withdraw prior to Month 3 are considered non-responders.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 31, 2019)
  • 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).
  • 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).
  • 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.
  • 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.
  • 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.
  • Mean change in serum uric acid from baseline to Weeks 14, 24, 36, 52 [ Time Frame: Baseline, Weeks 14, 24, 36, 52 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 15, 2018)
  • Proportion of Serum Uric Acid Responders (sUA < 6 mg/dL) at 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), and with at least one sUA level < 5 mg/dL anytime during the Dual Therapy Period after the first KRYSTEXXA® infusion. Participants who withdraw prior to Month 6 are considered non-responders.
  • 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), and with at least one sUA level < 5 mg/dL anytime during the Dual Therapy Period after the first KRYSTEXXA® infusion. Participants who withdraw prior to Month 3 or Month 6 are considered non-responders.
  • Proportion of Serum Uric Acid Responders (sUA < 5 mg/dL) at 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, (Weeks 10, 12,14). Participants who withdraw prior to Month 3 are considered non-responders.
  • Proportion of Serum Uric Acid Responders (sUA < 5 mg/dL) at 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, (Weeks 20, 22, 24). Participants who withdraw prior to Month 6 are considered non-responders.
  • 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, (Weeks 10,12,14, 20, 22, and 24). Participants who withdraw prior to Month 3 or Month 6 are considered non-responders.
  • Mean change from baseline in serum uric acid [ Time Frame: Baseline through week 24 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Pegloticase (KRYSTEXXA®) Plus Methotrexate in Patients With Uncontrolled Gout
Official Title  ICMJE A Multicenter, Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled GOut Receiving KRYSTEXXA® (Pegloticase) (MIRROR Open-Label [OL])
Brief Summary

This is a multicenter study of pegloticase (KRYSTEXXA®) given with methotrexate (MTX) in adult participants with uncontrolled gout. Approximately 12 to 14 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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Gout
Intervention  ICMJE 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)
Study Arms  ICMJE Experimental: Pegloticase with methotrexate (MTX) (single arm)
Participants will receive MTX during the run-in period and then pegloticase with MTX for 52 weeks
Intervention: Biological: Pegloticase with MTX
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 7, 2020)
14
Original Estimated Enrollment  ICMJE
 (submitted: August 15, 2018)
30
Estimated Study Completion Date  ICMJE December 2020
Actual Primary Completion Date October 23, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03635957
Other Study ID Numbers  ICMJE HZNP-KRY-201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Horizon Pharma Ireland, Ltd., Dublin Ireland ( Horizon Therapeutics Ireland DAC )
Study Sponsor  ICMJE Horizon Therapeutics Ireland DAC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Colleen Canavan, BS Horizon Therapeutics Ireland DAC
PRS Account Horizon Pharma Ireland, Ltd., Dublin Ireland
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP