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

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ClinicalTrials.gov Identifier: NCT03635957
Recruitment Status : Recruiting
First Posted : August 17, 2018
Last Update Posted : November 14, 2018
Sponsor:
Information provided by (Responsible Party):
Horizon Pharma Rheumatology LLC

Brief Summary:

This is a Phase 2, multicenter, study of KRYSTEXXA® (pegloticase) plus methotrexate (MTX) in adult participants with uncontrolled gout. Approximately 30 participants will be enrolled. Study duration will be approximately 32 weeks.

The purpose of this study is to assess the efficacy, safety, tolerability, and blood levels of concomitant use of KRYSTEXXA® and MTX immunosuppressive therapy, administered to prevent immunogenicity against KRYSTEXXA®, in adults with uncontrolled gout.


Condition or disease Intervention/treatment Phase
Gout Biological: KRYSTEXXA® Phase 2

Detailed Description:

This is a Phase 2, multicenter, study of KRYSTEXXA® (pegloticase) plus MTX in adult participants with uncontrolled gout.

The study design will include: 1) Screening Period which includes a MTX Run in Period; 2) 24 week Dual Therapy Period (KRYSTEXXA® + MTX); 3) an End of study/Early Termination Visit; 4) Safety Follow-up after last dose of KRYSTEXXA; and 5) For subjects that are non-vasectomized males; a 3- month follow up regarding partner pregnancy.

Interim analysis of the first 15 subjects will have the potential to influence the remainder of the study.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled GOut Receiving KRYSTEXXA® (Pegloticase) (MIRROR)
Actual Study Start Date : September 26, 2018
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

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

Arm Intervention/treatment
Experimental: KRYSTEXXA® with methotrexate (MTX)
All participants will receive dual therapy MTX and KRYSTEXXA®
Biological: KRYSTEXXA®
MTX lead-in and dual therapy MTX and KRYSTEXXA®
Other Name: methotrexate (MTX)




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  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), 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.

  3. 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.

  4. 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.

  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, (Weeks 10,12,14, 20, 22, and 24). Participants who withdraw prior to Month 3 or Month 6 are considered non-responders.

  6. Mean change from baseline in serum uric acid [ Time Frame: Baseline through week 24 ]


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 KRYSTEXXA® or at least one ovulatory cycle after the last dose of MTX (whichever is the longest duration after the last dose of KRYSTEXXA® 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 Dual Therapy 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 KRYSTEXXA®.

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 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 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


Contacts
Contact: Colleen Canavan, BS 866-479-6742 clinicaltrials@horizonpharma.com
Contact: Brenda Ranchino, BS 866-479-6742 clinicaltrials@horizonpharma.com

Locations
United States, Washington
Western Washington Arthritis Clinic Recruiting
Bothell, Washington, United States, 98021
Contact: Nicole Bruggman    425-248-2635    nbruggman@wwmedgroup.com   
Principal Investigator: Jeff R Peterson, MD         
Arthritis Northwest PLLC Recruiting
Spokane, Washington, United States, 99204
Contact: Terri Cone    509-838-6500 ext 310    tcone@arthritisnw.com   
Principal Investigator: Howard Kenney, MD         
Sponsors and Collaborators
Horizon Pharma Rheumatology LLC
Investigators
Study Director: Colleen Canavan, BS Horizon Pharma Rheumatology LLC

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: November 14, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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:
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