Tophaceous GoutPhase 1NCT06186219
Recapturing Immune Tolerance to Pegloticase for the Management of Tophaceous Gout
A Phase 1 study testing Rituximab in people with Tophaceous Gout, run by University of California, Los Angeles at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tophaceous Gout
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Apr 2024to 22 Nov 2024
- Phase
- Phase 1
- 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
- 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.
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- 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:
- 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.
Who cannot join
- 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).
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- 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.
- Contraindication to Methotrexate treatment or Methotrexate treatment considered inappropriate.
- Known intolerance to steroids, such as:
- History of steroid-induced Psychosis.
- History or steroid-induced diabetic ketoacidosis or hyperosmolar.
- Receipt of an investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to Methotrexate administration at Week -6 or plans to take an investigational drug during the study.
- Liver transaminase levels (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) > twice upper limit of normal (ULN) at the Screening Visit).
- Chronic liver disease.
- White blood cell count < 3,500/µL, hematocrit < 28 percent, or platelet count < 75,000/µL.
- Currently receiving systemic or radiologic treatment for ongoing cancer.
- History of malignancy within 5 years other than non-melanoma skin cancer or in situ carcinoma of cervix.
- Unsuitable candidate for the study, based on the opinion of the Investigator (e.g., cognitive impairment), such that participation might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements or complete the study.
- Alcohol use in excess of 1 alcoholic beverages per day.
- Current pulmonary fibrosis, bronchiectasis, or interstitial pneumonitis. If deemed necessary by the Investigator, a chest X-ray may be performed during Screening.
- Prior treatment with Rituximab (within 6 months) or Methotrexate (within 3 months).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
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.
Read the 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:
- Rituximab Pre-Treatment: up to 6-weeks + 1 week prior to Pegloticase treatment. (Pre-treatment of Rituximab will occur at -6 and -4 weeks.)
- 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).
- 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
- Being tested
- Rituximab
- Keywords
- gout, pegloticase, rituximab
- Medical subject headings
- Gout
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2023
- Study start10 Apr 2024
- Primary completion22 Nov 2024
- Study completion22 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tophaceous GoutStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John D. Fitzgerald, MD, PhD, University of California, Los Angeles
- Investigators
- John FitzGerald, MD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06186219
- Sponsor's protocol ID
- PEG study
- Status last verified
- Apr 2024
- First submitted
- 15 Dec 2023
- Last updated
- 20 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT06186219
- Acronym / sponsor ID
- PEG study
- Conditions
- Tophaceous Gout
- Keywords
- gout, pegloticase, rituximab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Study start
- 10 Apr 2024 (actual)
- Primary completion
- 22 Nov 2024 (actual)
- Study completion
- 22 Nov 2024 (actual)
- First posted
- 29 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Rituximab Pre-Treatment: up to 6-weeks + 1 week prior to Pegloticase treatment. (Pre-treatment of Rituximab will occur at -6 and -4 weeks.)
- 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).
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Experimental | Drug: RituximabRituximab 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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:
- Prior discontinued use of Pegloticase due to failure (rising SU > 6 mg/dL or history of moderate to severe infusion reaction).
Key exclusion criteria (29 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabRituximab 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. | Drug | Rituximab |
Primary outcome
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).
Time frame: 2 years
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.
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.
Time frame: 2 years
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John FitzGerald, MD principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Rituximab in people with Tophaceous Gout, run by University of California, Los Angeles at 1 site 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 13 inclusion and 29 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 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
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). (time frame: 2 years). 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?
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 20 Nov 2025.