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Trial record 1 of 1 for:    NCT02598596
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Tolerization Reduces Intolerance to Pegloticase and Prolongs the Urate Lowering Effect (TRIPLE)

This study is currently recruiting participants.
Verified November 2017 by Ampel BioSolutions, LLC
Sponsor:
ClinicalTrials.gov Identifier:
NCT02598596
First Posted: November 6, 2015
Last Update Posted: November 14, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
IND 2 Results LLC
Information provided by (Responsible Party):
Ampel BioSolutions, LLC
  Purpose
The purpose of this study is to evaluate the effect of a high zone tolerizing regimen of pegloticase on clinical outcome, as defined by an serum uric acid level <6 mg/dL, in patients with chronic, refractory gout.

Condition Intervention Phase
Gout Biological: Pegloticase Drug: Azathioprine Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Tolerization Reduces Intolerance to Pegloticase and Prolongs the Urate Lowering Effect

Resource links provided by NLM:


Further study details as provided by Ampel BioSolutions, LLC:

Primary Outcome Measures:
  • Normalization of serum uric acid (SUA) in subjects receiving a tolerizing regimen of pegloticase [ Time Frame: Week 17 ]
    Determine response rate; the last 3 consecutive levels of SUA must be <6 mg/dL

  • Normalization of serum uric acid (SUA) in subjects receiving pegloticase and azathioprine (AZA) immunosuppressive therapy [ Time Frame: Week 25 ]
    Determine response rate; the last 3 consecutive levels of SUA must be <6 mg/dL


Secondary Outcome Measures:
  • Change from baseline in SUA to end of Treatment [ Time Frame: Baseline and Week 17 ]
    Change from baseline

  • Change from baseline in SUA to end of Treatment [ Time Frame: Baseline and Week 25 ]
    Change from baseline - AZA arm

  • Proportion of subjects with SUA <5 mg/dL [ Time Frame: Week 17 ]
    Proportion of subjects

  • Proportion of subjects with SUA <5 mg/dL [ Time Frame: Week 25 ]
    Proportion of subjects - AZA arm

  • Proportion of subjects with SUA <2 mg/dL [ Time Frame: Week 17 ]
    Proportion of subjects

  • Proportion of subjects with SUA <2 mg/dL [ Time Frame: Week 25 ]
    Proportion of subjects - AZA arm

  • Infusion reactions (IRs) and anaphylaxis [ Time Frame: Week 17 ]
    Incidence - AZA arm

  • Infusion reactions (IRs) and anaphylaxis [ Time Frame: Week 25 ]
    Incidence

  • Incidence of anti-pegloticase antibodies [ Time Frame: Week 17 ]
    Anti-pegloticase antibodies

  • Incidence of anti-pegloticase antibodies [ Time Frame: Week 25 ]
    Anti-pegloticase antibodies - AZA arm

  • Mean titer of anti-pegloticase antibodies [ Time Frame: Week 17 ]
    Anti-pegloticase antibodies

  • Mean titer of anti-pegloticase antibodies [ Time Frame: Week 25 ]
    Anti-pegloticase antibodies AZA arm

  • Incidence of gout flares, adverse events (AEs), serious AEs (SAEs), and early terminations due to AEs [ Time Frame: Week 17 ]
    Incidence

  • Incidence of gout flares, adverse events (AEs), serious AEs (SAEs), and early terminations due to AEs [ Time Frame: Week 25 ]
    Incidence - AZA arm


Other Outcome Measures:
  • Relationship in change from baseline in SUA from baseline with rate of infusion reactions [ Time Frame: Baseline to Week 17 ]
    Correlation between change in SUA and infusion reactions

  • Relationship in change from baseline in SUA from baseline with rate of infusion reactions [ Time Frame: Baseline to Week 25 ]
    Correlation between change in SUA and infusion reactions - AZA arm

  • Compare trough pegloticase levels [ Time Frame: Week 17 ]
    Descriptive statistics

  • Compare trough AZA levels [ Time Frame: Week 25 ]
    Descriptive statistics

  • Ability of imaging to monitor treatment response [ Time Frame: Baseline and Week 17 ]
    To compare the ability of dual-energy computed tomography (DECT) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to monitor treatment response, in a subset of subjects weighing < 120 kg

  • Evaluate change from baseline carotid and aortic (chest) atherosclerosis [ Time Frame: Baseline and Week 17 ]
    Change from baseline as measured by fluorodeoxyglucose-positron emission tomography (FDG-PET-CT), in a subset of subjects weighing < 120 kg

  • Cmax of pegloticase in subjects weighing ≥ 120 kg and < 120 kg [ Time Frame: Up to Week 17 ]
    PK parameter

  • Tmax of pegloticase in subjects weighing ≥ 120 kg and < 120 kg [ Time Frame: Up to Week 17 ]
    PK parameter

  • AUC of pegloticase in subjects weighing ≥ 120 kg and < 120 kg [ Time Frame: Up to Week 17 ]
    PK parameter

  • Terminal phase half-life of pegloticase in subjects weighing ≥ 120 kg and < 120 kg [ Time Frame: Up to Week 17 ]
    PK parameter

  • CL of pegloticase in subjects weighing ≥ 120 kg and < 120 kg [ Time Frame: Up to Week 17 ]
    PK parameter

  • Vss of pegloticase in subjects weighing ≥ 120 kg and < 120 kg [ Time Frame: Up to Week 17 ]
    PK parameter

  • Accumulation Ratio (AR) of pegloticase in subjects weighing ≥ 120 kg and < 120 kg [ Time Frame: Up to Week 17 ]
    PK parameter


Estimated Enrollment: 177
Actual Study Start Date: December 2015
Estimated Study Completion Date: April 2020
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pegloticase regimen <120 kg - Main Study
Subjects weighing <120 kg will receive a tolerizing dose of pegloticase 8 mg IV weekly for the first 3 weeks of dosing followed by an 8 mg IV dose every 2 weeks for a total of 10 doses.
Biological: Pegloticase
Pegloticase, IV
Other Name: Krystexxa
Experimental: Pegloticase regimen ≥120kg
Subjects weighing ≥ 120 kg will be sequentially assigned to 1 of 3 different loading doses (8, 12, and 16 mg) on Study Day 1, and then receive 8 mg on Week 2 and 3, followed by 8 mg every 2 weeks through Week 17 for a total of 10 doses.
Biological: Pegloticase
Pegloticase, IV
Other Name: Krystexxa
Experimental: Pegloticase PK Sub-Study
Subjects weighing <120 kg and ≥120 kg will be assigned to 1 of 2 different loading doses (12 and 16 mg) on Study Day 1, and then receive 8 mg on Week 2 and 3, followed by 8 mg every 2 weeks through Week 17 for a total of 10 doses. Subjects will have multiple blood sampled for PK levels over the 17 week dosing period.
Biological: Pegloticase
Pegloticase, IV
Other Name: Krystexxa
Experimental: Pegloticase Imaging Sub-Study
A subset of subjects participating in the Main Study and weighing <120 kg will have dual-energy computed tomography (DECT) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) performed at Screen and at Week 17.
Biological: Pegloticase
Pegloticase, IV
Other Name: Krystexxa
Experimental: Pegloticase FDG-PET-CT Sub-Study
A subset of subjects participating in the Main Study and weighing <120 kg will have fluorodeoxyglucose-positron emission tomography (FDG-PET-CT) to evaluate carotid and aortic (chest) atherosclerosis at Screen and at Week 17.
Biological: Pegloticase
Pegloticase, IV
Other Name: Krystexxa
Experimental: Pegloticase and Azathioprine
Subjects weighing <120 kg will receive azathioprine (AZA) daily for a 2-week run-in period, followed by daily AZA plus pegloticase 8 mg IV every 2 weeks through Week 25 for a total of 13 doses.
Biological: Pegloticase
Pegloticase, IV
Other Name: Krystexxa
Drug: Azathioprine
Azathioprine (1.25 mg/kg, followed by 2.5 mg/kg) oral, daily
Other Name: Imuran

Detailed Description:

This is an exploratory open-label, multicenter study to evaluate the effectiveness of a 16-week high zone tolerance regimen of pegloticase on response to therapy (serum uric acid <6 mg/dL) with this drug in adult hyperuricemic patients with gout refractory to conventional therapy.

Eligible subjects will receive 1 of 3 different loading doses (8, 12, and 16 mg) on Study Day 1, and then receive 8 mg on Week 2 and 3, followed by 8 mg every 2 weeks through Week 17 for a total of 10 doses.

Subjects will be monitored for efficacy and safety endpoints through Week 17. Subjects will also have blood drawn for pegloticase levels prior to each dose on Weeks 2, 3, 5, 7, 9, 11, 13,15, and 17. Following Study Week 17, subjects will have an option to continue dosing for an additional 8 weeks.

A subset of subjects will participate in additional pharmacokinetic (PK) assessments.

The study duration, per enrolled patient, will be approximately 26 weeks including a 2-week screening period, a 16-week treatment period (end of treatment [EOT] visit Week 17), and an optional 8-week dosing extension.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult (age ≥18 years) men and women of non-childbearing potential, with chronic gout refractory to conventional therapy, defined as patients who have failed to normalize SUA and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose, or for whom these drugs are contraindicated.
  2. Hyperuricemic - Screening visit SUA must be >6 mg/dL
  3. On gout flare prophylactic regimen for 7 days prior to the first dose.
  4. Willing and able to give informed consent and adhere to visit/protocol schedules (informed consent must be given before the first study procedure is performed)

Exclusion Criteria:

  1. Glucose-6-phosphate dehydrogenase (G6PD) deficiency (confirmed at Screening visit)
  2. Non-compensated congestive heart failure, uncontrolled arrhythmia, treatment for acute coronary syndrome (ACS) (myocardial infarction or unstable angina) or hospitalization for congestive heart failure within 3 months of screening or uncontrolled blood pressure (>160/100 mm Hg) at baseline (Screening and pre-dose at Week 1 visit )
  3. Women of childbearing potential defined as:

    • Pre- or perimenopausal (<24 months of natural [spontaneous] amenorrhea).
    • <6 weeks after surgical bilateral oophorectomy with or without hysterectomy.
  4. Prior treatment with pegloticase or another recombinant uricase
  5. Prior treatment or concomitant therapy with a polyethylene glycol (PEG) conjugated drug
  6. Known allergy to PEG products or history of anaphylactic reaction to a recombinant protein or porcine product
  7. Concurrent treatment with urate lowering agents (ULAs), such as allopurinol and febuxostat. Patients treated with these medications must discontinue treatment 7 days prior to the first dose of study drug
  8. Recipient of an investigational drug within 4 weeks prior to study drug administration or plans to take an investigational agent during the study
  9. Current liver disease as determined by alanine transaminase (ALT) or aspartate transaminase (AST) levels >3 times upper limit of normal (ULN)
  10. History of malignancy within 5 years other than basal cell skin cancer or carcinoma in situ of the cervix
  11. Has any other medical or psychological condition which, in the opinion of the Investigator, might create undue risk to the patient or interfere with the patient's ability to comply with the protocol requirements, or to complete the study
  12. Solid organ transplant recipients
  13. Uncontrolled hyperglycemia with a plasma glucose value >240 mg/dL at screening
  14. Currently on dialysis

    Additional Exclusion Criteria for Imaging Sub-study Only

  15. Contraindication to receiving a gadolinium-based contrast agent (GBCA) or > 2 previous lifetime exposures to a GBCA
  16. Implanted pacemaker, certain older intracranial aneurysm clips, cochlear implants, certain prosthetic devices, implanted drug infusion pumps, neurostimulators, bone-growth stimulators, certain intrauterine contraceptive devices, or any other type of iron-based metal implants.
  17. Any internal metallic objects such as bullets or shrapnel, as well as most surgical clips, pins, plates, screws, metal sutures, or wire mesh.

    Additional Exclusion Criteria for FDG-PET-CT Sub-study Only

  18. Contraindication to FDG

    Additional Exclusion Criteria for Pegloticase and AZA Therapy Arm Only

  19. Any active serious bacterial infection (2 weeks prior to screening) requiring antibiotic treatment
  20. Severe chronic or recurrent bacterial infections, such as recurrent pneumonia, chronic bronchiectasis
  21. Current immunocompromised condition, including current or chronic treatment with systemic immunosuppressive agents (e.g., prednisone or equivalent dose >510 mg/day)
  22. At risk for tuberculosis. Specifically, subjects with: a) current clinical, radiographic, or laboratory evidence of active or latent tuberculosis; b) a history of active tuberculosis within the last 31 years even if it was treated; c) a history of active tuberculosis >31 years ago unless there is documentation that the prior anti-tuberculosis treatment was appropriate in duration and type
  23. Known history of hepatitis B surface antigen-positivity or hepatitis B DNA positivity
  24. Known history of hepatitis C RNA-positivity
  25. Known history of human immunodeficiency virus positivity
  26. Severe chronic renal impairment (glomerular filtration rate <25 mL/min/1.73 m2)
  27. AZA treatment is contraindicated or considered inappropriate
  28. Subject has a homozygous or heterozygous thiopurine methyltransferase (TPMT) variant genotype
  29. Diagnosis of osteomyelitis
  30. Known hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome
  31. Concurrent use of a xanthine oxidase inhibitor
  Contacts and Locations
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): NCT02598596


Contacts
Contact: Maggie Pugh, MS 404-892-7002 mpugh@ind2results.com

Locations
United States, Alabama
University of Alabama at Birminingham Recruiting
Birmingham, Alabama, United States, 35294
Rheumatology Associates of North Alabama Recruiting
Huntsville, Alabama, United States, 35801
United States, California
Pacific Arthritis Center Medical Group Withdrawn
Santa Maria, California, United States, 93454
United States, Maryland
The Center for Rheumatology and Bone Research Recruiting
Wheaton, Maryland, United States, 20902
United States, Massachusetts
Clinical Pharmacology Study Group Recruiting
Worcester, Massachusetts, United States, 01609
United States, Michigan
Henry Ford Health System Recruiting
Detroit, Michigan, United States, 48202
United States, Minnesota
Saint Paul Rheumatology Recruiting
Eagan, Minnesota, United States, 55121
United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467
Buffalo Rheumatology and Medicine Recruiting
Orchard Park, New York, United States, 14127
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Altoona Center for Clinical Research Recruiting
Duncansville, Pennsylvania, United States, 16635
United States, South Carolina
ACME Research, LLC Recruiting
Orangeburg, South Carolina, United States, 29118
Sponsors and Collaborators
Ampel BioSolutions, LLC
IND 2 Results LLC
  More Information

Responsible Party: Ampel BioSolutions, LLC
ClinicalTrials.gov Identifier: NCT02598596     History of Changes
Other Study ID Numbers: AMP-001
First Submitted: October 30, 2015
First Posted: November 6, 2015
Last Update Posted: November 14, 2017
Last Verified: November 2017

Keywords provided by Ampel BioSolutions, LLC:
Refractory gout
Chronic gout

Additional relevant MeSH terms:
Azathioprine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents