NCT06186219

Recapturing Immune Tolerance to Pegloticase for the Management of Tophaceous Gout

Open-label Study of Rituximab (RTX) Pretreatment Followed by Standard of Care (SOC) Methotrexate-Pegloticase (MTXPEG) to Treat Poorly Controlled Tophaceous Gout in Individuals With Prior Loss of Response to Pegloticase.

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: University of California, Los Angeles · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Rituximab 1000 mg will be administered at week -6 and week -4 via intravenous infusion over the duration of 5 hours prior to Methotrexate-Pegloticase Standard-of-Care treatment. Per FDA approved dosing in the package insert, Rituximab infusion with concentration of 10 mg/mL will begin at 50 mg/hr. In the absence of infusion toxicity, increase infusion rate by 50 mg/hour increments every 30 minutes, to a maximum of 400 mg/hour or total dose of 1000 mg. All subjects will be treated with Methotrexate-Pegloticase Standard-of-Care with FDA-approved dosing of Pegloticase 8 mg IV infusion every 2 weeks, co-administered with methotrexate 15 mg orally once weekly (started 4 weeks prior to Pegloticase initiation). Standard-of-Care includes Pegloticase infusion every 2 weeks as long as clinically indicated (e.g., persistent tophus), concluding treatment when all tophaceous gout lesions resolve or up to 12-months, safety stop point, or subject withdrawal from the study. Subjects will be on study for up to 24 months. Screening visit: up to 28-days. Treatment visit: 1. Rituximab Pre-Treatment: up to 6-weeks + 1 week prior to Pegloticase treatment. (Pre-treatment of Rituximab will occur at -6 and -4 weeks.) 2. Methotrexate Treatment (Standard-of-Care): up to 6 weeks + 1 week prior to Pegloticase treatment. (Administered four weeks prior to Pegloticase and weekly during Pegloticase treatment). 3. Methotrexate-Pegloticase Study Treatment (Standard-of-Care): up to 12 months of Standard-of-Care. (Methotrexate is administered weekly and Pegloticase is coadministered every two weeks). Follow-up phone visits: up to 30 and 60 days after last dose of Methotrexate-Pegloticase + 7 days. Total subject participation duration is up to 24 months. Total study duration for recruitment, enrollment, and study completion of all subjects is up to 5 years.

Conditions

• Tophaceous Gout

Interventions

Type	Name	Description
DRUG	Rituximab	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.

Timeline

• Start date: 2024-04-10
• Primary completion: 2024-11-22
• Completion: 2024-11-22
• First posted: 2023-12-29
• Last updated: 2025-11-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study