Tolerization Reduces Intolerance to Pegloticase and Prolongs the Urate Lowering Effect

NCT02598596 | Completed Phase 2

• 1 other identifier: AMP-001
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Gout

Keywords

Refractory gout; Chronic gout

Outcome Measures

Primary Outcomes (2)

• 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

  Week 17

• 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

  Week 25

Secondary Outcomes (14)

• Change from baseline in SUA to end of Treatment

  Baseline and Week 17

• Change from baseline in SUA to end of Treatment

  Baseline and Week 25

• Proportion of subjects with SUA <5 mg/dL

  Week 17

• Proportion of subjects with SUA <5 mg/dL

  Week 25

• Proportion of subjects with SUA <2 mg/dL

  Week 17

Other Outcomes (13)

• Relationship in change from baseline in SUA from baseline with rate of infusion reactions

  Baseline to Week 17

• Relationship in change from baseline in SUA from baseline with rate of infusion reactions

  Baseline to Week 25

• Compare trough pegloticase levels

  Week 17

Study Arms (6)

Pegloticase regimen <120 kg - Main Study

EXPERIMENTAL

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 regimen ≥120kg

EXPERIMENTAL

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 PK Sub-Study

EXPERIMENTAL

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 Imaging Sub-Study

EXPERIMENTAL

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 FDG-PET-CT Sub-Study

EXPERIMENTAL

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 and Azathioprine

EXPERIMENTAL

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; Drug: Azathioprine

Interventions

Pegloticase BIOLOGICAL

Pegloticase, IV

Also known as: Krystexxa

Pegloticase FDG-PET-CT Sub-Study; Pegloticase Imaging Sub-Study; Pegloticase PK Sub-Study; Pegloticase and Azathioprine; Pegloticase regimen <120 kg - Main Study; Pegloticase regimen ≥120kg

Azathioprine DRUG

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

Also known as: Imuran

Pegloticase and Azathioprine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Ampel BioSolutions, LLC: lead
• IND 2 Results LLC: collaborator

Study Sites (11)

University of Alabama at Birminingham

Birmingham, Alabama, 35294, United States

Location

Rheumatology Associates of North Alabama

Huntsville, Alabama, 35801, United States

Location

The Center for Rheumatology and Bone Research

Wheaton, Maryland, 20902, United States

Location

Clinical Pharmacology Study Group

Worcester, Massachusetts, 01609, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Saint Paul Rheumatology

Eagan, Minnesota, 55121, United States

Location

Buffalo Rheumatology and Medicine

Orchard Park, New York, 14127, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

ACME Research, LLC

Orangeburg, South Carolina, 29118, United States

Location

MeSH Terms

Conditions

Gout

Interventions

Pegloticase; Azathioprine

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2015
• First Posted: November 6, 2015
• Study Start: December 1, 2015
• Primary Completion: April 13, 2020
• Study Completion: April 27, 2020
• Last Updated: October 11, 2021

Record last verified: 2021-10

Locations

US (11)