Recapturing Immune Tolerance to Pegloticase for the Management of Tophaceous Gout

NCT06186219 | Completed Phase 1 FDA Drug

• 1 other identifier: PEG study
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This safety and feasibility, open-label study of up to 9 subjects will examine a group of subjects with poorly controlled tophaceous gout (intolerant to or ineffective oral urate lowering agents and loss of prior Pegloticase response) pre-treated with Rituximab to recapture response to Methotrexate-Pegloticase.

Conditions

Tophaceous Gout

Keywords

gout; pegloticase; rituximab

Outcome Measures

Primary Outcomes (2)

• The study will be measured by the frequency and grade of adverse event (AEs) (solicited and unsolicited), serious adverse experience (SAEs), adverse event of special interest (AESI1s), medically attended adverse events (MAAEs).

  Simple descriptive statistics will be used to summarize toxicities in terms of type, severity and minimum or maximum values for laboratory measures, time of onset, duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects. Safety Analyses will be performed on Safety Analysis Set. After the first Pegloticase infusion, any subsequent pre-Pegloticase infusion lab result of serum urate \> 6 mg/dL will terminate the study.

  2 years

• Neutralizing antibody titers (assays provided by Horizon labs) will be measured at Screening (Visit 0), prior to first Pegloticase infusion (Visit 3, Week 0), Visit 9, Week 12 and Visit 16, Week 26.

  Mean change between baseline and the specified follow up measurements will be analyzed using general linear modelling with adjustment to control for within person correlation of repeated measurements.

  2 years

Study Arms (1)

Rituximab

EXPERIMENTAL

Rituximab 1000 mg will be administered at week -6 and week -4 via intravenous infusion over the duration of 5 hours prior to the Pegloticase (Standard-of-Care) treatment.

Drug: Rituximab

Interventions

Rituximab DRUG

Rituximab is a monoclonal antibody that targets cluster of differentiate 20 (CD20) present on B-cells and lowers humoral immunity. Rituximab has been used successfully as a desensitization agent to treat Highly Human Leukocyte Antigens (HLA)-sensitized patients planning renal transplant. All cases of antibody-mediated rejection were seen in the placebo group, none in the Rituximab group. Rituximab has been safely used with Methotrexate in the treatment of Rheumatoid Arthritis, where co-administration of Methotrexate and Rituximab results in better outcomes than either medication alone. We propose this safety and feasibility open-label trial that will examine if Rituximab pre-treatment before Standard-of-Care Methotrexate-Pegloticase will result in recapture of Pegloticase efficacy as measured by serum urate (SU) \< 6 mg/dL throughout the trial and up to 6-months of Methotrexate-Pegloticase administration.

Rituximab

Eligibility Criteria

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

You may qualify if:

• Eligible subjects must meet/provide all the following criteria:
• Must be able to provide written informed consent.
• Male or female ≥ 18 years of age at Baseline Visit.
• Meets the American College of Rheumatology Classification Criteria for Gout.
• Poorly controlled tophaceous gout, defined as meeting the following criteria:
• Hyperuricemia during the screening period defined as serum urate ≥ 6 mg/dL.
• Failure to maintain normalization of serum urate with xanthine oxidase inhibitors at the maximum medically appropriate dose, or with a contraindication to xanthine oxidase inhibitor therapy based on medical record review or subject interview, and;
• Symptoms of gout including at least 1 of the following:
• i. Presence of at least one tophus. ii. Recurrent flares defined as 2 or more flares in the past 12 months prior to screening.
• Prior discontinued use of Pegloticase due to failure (rising SU \> 6 mg/dL or history of moderate to severe infusion reaction).
• Normal Glucose-6-phosphate dehydrogenase levels.
• Willing to discontinue any oral urate lowering therapy for at least 7 days prior to first Pegloticase infusion and remain off therapy when receiving Pegloticase infusions.
• 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 Screening and Week 0; subjects must agree to use reliable form of contraception during the study. Hormonal contraception must be continued while on Methotrexate. 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.

You may not qualify if:

• Subjects will be ineligible for trial participation if they meet any of the following criteria:
• Glucose-6-phosphate dehydrogenase deficiency (documented or tested at the Screening Visit).
• Chronic renal impairment defined as estimated glomerular filtration rate (epidermal growth factor receptor) \< 30 mL/min/1.73 m2 or currently on dialysis.
• Non-compensated congestive heart failure (stage C) 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).
• Uncontrolled blood pressure (\>160/100 mmHg) prior to Rituximab infusion (week -6, week -4).
• On treatment for current non-skin cell cancer.
• Any serious acute bacterial infection, unless treated and completely resolved with antibiotics at least 2 weeks prior to the Week -6 Visit.
• Severe chronic or recurrent bacterial infections, such as recurrent pneumonia or chronic bronchiectasis.
• Anaphylaxis or other prior severe infusion reaction to Pegloticase that the study allergy-immunologist deems treatment with Pegloticase to be unsafe to rechallenge.
• History of any transplant surgery requiring maintenance immunosuppressive therapy.
• Known history of hepatitis B virus surface antigen positivity or hepatitis B DNA positivity.
• Known history of hepatitis C virus ribonucleic acid (RNA) positivity.
• Known history of Human Immunodeficiency Virus (HIV) positivity.
• Pregnant, planning to become pregnant, breastfeeding, or not on an effective form of birth control, as determined by the Investigator.

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

UCLA

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Gout

Interventions

Rituximab

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)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• John FitzGerald, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clin Prof, Clinical Chief

Study Record Dates

• First Submitted: December 15, 2023
• First Posted: December 29, 2023
• Study Start: April 10, 2024
• Primary Completion: November 22, 2024
• Study Completion: November 22, 2024
• Last Updated: November 20, 2025

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)