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GoutPhase 2TRIPLENCT02598596

Tolerization Reduces Intolerance to Pegloticase and Prolongs the Urate Lowering Effect

A Phase 2 study testing Pegloticase and Azathioprine in people with Gout, run by Ampel BioSolutions, LLC at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Gout
What is being tested?
Pegloticase and Azathioprine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
132 participants
Where
11 sitesUnited States
Study dates
Dec 2015to 27 Apr 2020
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • Hyperuricemic - Screening visit SUA must be >6 mg/dL
  • On gout flare prophylactic regimen for 7 days prior to the first dose.
  • 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)

Who cannot join

  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency (confirmed at Screening visit)
  • 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 )
  • 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.
  • Prior treatment with pegloticase or another recombinant uricase
Show all 36Show fewer
  • Prior treatment or concomitant therapy with a polyethylene glycol (PEG) conjugated drug
  • Known allergy to PEG products or history of anaphylactic reaction to a recombinant protein or porcine product
  • 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
  • Recipient of an investigational drug within 4 weeks prior to study drug administration or plans to take an investigational agent during the study
  • Current liver disease as determined by alanine transaminase (ALT) or aspartate transaminase (AST) levels >3 times upper limit of normal (ULN)
  • History of malignancy within 5 years other than basal cell skin cancer or carcinoma in situ of the cervix
  • 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
  • Solid organ transplant recipients
  • Uncontrolled hyperglycemia with a plasma glucose value >240 mg/dL at screening
  • Currently on dialysis
  • Additional Exclusion Criteria for Imaging Sub-study Only
  • Contraindication to receiving a gadolinium-based contrast agent (GBCA) or > 2 previous lifetime exposures to a GBCA
  • 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.
  • 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
  • Contraindication to FDG
  • Additional Exclusion Criteria for Pegloticase and AZA Therapy Arm Only
  • Any active serious bacterial infection (2 weeks prior to screening) requiring antibiotic treatment
  • Severe chronic or recurrent bacterial infections, such as recurrent pneumonia, chronic bronchiectasis
  • Current immunocompromised condition, including current or chronic treatment with systemic immunosuppressive agents (e.g., prednisone or equivalent dose >510 mg/day)
  • 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
  • Known history of hepatitis B surface antigen-positivity or hepatitis B DNA positivity
  • Known history of hepatitis C RNA-positivity
  • Known history of human immunodeficiency virus positivity
  • Severe chronic renal impairment (glomerular filtration rate <25 mL/min/1.73 m2)
  • AZA treatment is contraindicated or considered inappropriate
  • Subject has a homozygous or heterozygous thiopurine methyltransferase (TPMT) variant genotype
  • Diagnosis of osteomyelitis
  • Known hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome
  • Concurrent use of a xanthine oxidase inhibitor

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • University of Alabama at Birminingham

    Birmingham, Alabama, 35294

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Altoona Center for Clinical Research

    Duncansville, Pennsylvania, 16635

  • Saint Paul Rheumatology

    Eagan, Minnesota, 55121

  • Rheumatology Associates of North Alabama

    Huntsville, Alabama, 35801

  • ACME Research, LLC

    Orangeburg, South Carolina, 29118

  • Buffalo Rheumatology and Medicine

    Orchard Park, New York, 14127

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • The Center for Rheumatology and Bone Research

    Wheaton, Maryland, 20902

  • Clinical Pharmacology Study Group

    Worcester, Massachusetts, 01609

Other trials in United States

About this study

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.

Read the 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.

Conditions
Gout
Being tested
Pegloticase, Azathioprine
Keywords
Refractory gout, Chronic gout
Medical subject headings
Gout

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PegloticaseBiological

    Also called Krystexxa

    Pegloticase, IV

  • AzathioprineDrug

    Also called Imuran

    Azathioprine (1.25 mg/kg, followed by 2.5 mg/kg) oral, daily

Study groups in NCT02598596
Study groupRoleWhat they receive
Pegloticase regimen <120 kg - Main StudyExperimentalSubjects 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.
Receives: Biological: Pegloticase
Pegloticase regimen ≥120kgExperimentalSubjects 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.
Receives: Biological: Pegloticase
Pegloticase PK Sub-StudyExperimentalSubjects 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.
Receives: Biological: Pegloticase
Pegloticase Imaging Sub-StudyExperimentalA 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.
Receives: Biological: Pegloticase
Pegloticase FDG-PET-CT Sub-StudyExperimentalA 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.
Receives: Biological: Pegloticase
Pegloticase and AzathioprineExperimentalSubjects 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.
Receives: Biological: Pegloticase; Drug: Azathioprine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Normalization of serum uric acid (SUA) in subjects receiving a tolerizing regimen of pegloticase

    Determine response rate; the last 3 consecutive levels of SUA must be <6 mg/dL

    Measured: Week 17

  2. Normalization of serum uric acid (SUA) in subjects receiving pegloticase and azathioprine (AZA) immunosuppressive therapy

    Determine response rate; the last 3 consecutive levels of SUA must be <6 mg/dL

    Measured: Week 25

Secondary outcomes (14)

  1. Change from baseline in SUA to end of Treatment

    Change from baseline

    Measured: Baseline and Week 17

  2. Change from baseline in SUA to end of Treatment

    Change from baseline - AZA arm

    Measured: Baseline and Week 25

  3. Proportion of subjects with SUA <5 mg/dL

    Proportion of subjects

    Measured: Week 17

  4. Proportion of subjects with SUA <5 mg/dL

    Proportion of subjects - AZA arm

    Measured: Week 25

  5. Proportion of subjects with SUA <2 mg/dL

    Proportion of subjects

    Measured: Week 17

  6. Proportion of subjects with SUA <2 mg/dL

    Proportion of subjects - AZA arm

    Measured: Week 25

  7. Infusion reactions (IRs) and anaphylaxis

    Incidence - AZA arm

    Measured: Week 17

  8. Infusion reactions (IRs) and anaphylaxis

    Incidence

    Measured: Week 25

  9. Incidence of anti-pegloticase antibodies

    Anti-pegloticase antibodies

    Measured: Week 17

  10. Incidence of anti-pegloticase antibodies

    Anti-pegloticase antibodies - AZA arm

    Measured: Week 25

  11. Mean titer of anti-pegloticase antibodies

    Anti-pegloticase antibodies

    Measured: Week 17

  12. Mean titer of anti-pegloticase antibodies

    Anti-pegloticase antibodies AZA arm

    Measured: Week 25

  13. Incidence of gout flares, adverse events (AEs), serious AEs (SAEs), and early terminations due to AEs

    Incidence

    Measured: Week 17

  14. Incidence of gout flares, adverse events (AEs), serious AEs (SAEs), and early terminations due to AEs

    Incidence - AZA arm

    Measured: Week 25

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Nov 2015 (estimated)
  2. Study startDec 2015
  3. Primary completion13 Apr 2020
  4. Study completion27 Apr 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
132 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02598596
Sponsor's protocol ID
AMP-001
Acronym
TRIPLE
Status last verified
Oct 2021
First submitted
30 Oct 2015
Last updated
11 Oct 2021
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pegloticase and Azathioprine in people with Gout, run by Ampel BioSolutions, LLC at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Normalization of serum uric acid (SUA) in subjects receiving a tolerizing regimen of pegloticase (time frame: Week 17). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02598596.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Oct 2021.

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