A Phase Ib Clinical Trial of Peguricase for Injection With Methotrexate in Patients With Uncontrolled Gout.

NCT06298071 | Recruiting Phase 1 DMC

• 1 other identifier: SIBP-R002-Ib
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the safety and tolerability of peguricase for injection with methotrexate in patients with gout who remain uncontrolled after standardized treatment with conventional uric acid-lowering drugs, to determine the recommended dose for phase II clinical trials, and to provide basis for formulation of administration regimen for phase II clinical trials.

Conditions

Gout

Keywords

Uncontrolled gout; Peguricase for injection; Safety; Tolerability; Efficacy

Outcome Measures

Primary Outcomes (9)

• AE(Adverse Events)

  That is adverse events, any adverse events that occurred to the participant during the study period.

  14 weeks after the first dose

• SAE(Serious Adverse Events)

  That is serious adverse events, any serious adverse events that occurred to the participant during the study period.

  14 weeks after the first dose

• AUC(Area Under The Plasma Concentration Versus Time Curve)

  It shows the degree to which a drug is absorbed and used in the body

  14 weeks after the first dose

• Cmax(Peak Plasma Concentration)

  It shows the highest plasma concentration of a drug that can be achieved after administration.

  14 weeks after the first dose

• Tmax(Peak Time)

  That is peak time of drug action, it shows the time required to reach the maximum concentration on the participant plasma concentration curve after administration.

  14 weeks after the first dose

• T ½ (Terminal elimination half-life)

  It reflects how quickly the drug is eliminated from the body.

  14 weeks after the first dose

• CL (Clearance Rate)

  Apparent volume of drug distribution removed from the body per unit time.

  14 weeks after the first dose

• ADA (Anti-uricase Antibody, Anti-PEG Antibody, Anti-PEG-uricase Antibody)

  The incidence of anti-drug antibody.

  14 weeks after the first dose

• NAb (Anti-PEG-uricase Neutralizing Antibody)

  The incidence of neutralizing antibody.

  14 weeks after the first dose

Study Arms (3)

Group 1

EXPERIMENTAL

Injection; strength: 4mg.

Drug: SIBP-R002; Drug: Methotrexate

Group 2

EXPERIMENTAL

Injection; strength: 8mg.

Drug: SIBP-R002; Drug: Methotrexate

Group 3

EXPERIMENTAL

Injection; strength: 12mg.

Drug: SIBP-R002; Drug: Methotrexate

Interventions

SIBP-R002 DRUG

Injection; strength: 4mg. Each group consists of 12 participants. Firstly, 4 sentinel participants were enrolled in the single dose phase of peruricase for injection and methotrexate. After the sentinel participants completed a 5-day safety observation of the single dose, the remaining 8 participants in this group can be enrolled simultaneously. If there are no special circumstances, the participants in this group will enter the multi-dose stage of peruricase for injection combined with methotrexate within 2-4 weeks after completing a single dose.

Also known as: Peguricase for injection

Group 1

Methotrexate DRUG

Combination drugs: Methotrexate, dose15 mg, oral.

Group 1; Group 2; Group 3

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to give informed consent.
• Male and female aged between 18 and 70 years old , regardless of gender.
• Male weight ≥50 kg, female weight ≥45 kg, body mass index (BMI) in the range of (19-30) kg/m2 (including 19 and 30)；
• The clinical diagnosis of gout met the criteria of American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) in 2015，patients were in non-acute attack at screening or at least 2 weeks after complete remission of acute attack, and sUA ≥420 μmol/L at screening；
• Patients whose serum uric acid level could not reach the target after standard treatment with conventional uric acid-lowering drugs or who were contraindicated or intolerant to conventional uric acid-lowering drugs；
• Patients who were willing to stop taking any uric-acid-lowering drug at least 7 days before using methotrexate during the run-in period;
• Could tolerate the prescribed dose of methotrexate during the run-in period;
• Patients were able to attend and complete the visit on time.

You may not qualify if:

• Patients had active systemic infection within 2 weeks before enrollment，including an infection for which treatment was being received；
• Having a chronic or recurrent infection, such as recurrent pneumonia or chronic bronchitis; Patients with active or severe lung disease or pulmonary insufficiency on chest imaging, or current pulmonary fibrosis or bronchiectasis；
• Patients who are on anti-TB treatment or have active TB；
• Diagnosis of osteomyelitis；
• Ongoing or long-term use of immune system modulating drugs, such as methotrexate, mercaptopurine, mycophanolate, long-term use (≥3 months) of prednisone ≥10 mg/ day or equivalent dose of corticosteroids; Or have a history of transplant surgery requiring long-term immunotherapy; Or a known history of autoimmune disease, allergic disease;
• Known allergy to recombinant proteins or porcine products, or history of allergy to uricase, pegylated products, corticosteroids and antihistamines, or known intolerance to methotrexate, fexofenadine, acetaminophen or contraindications to methotrexate, fexofenadine, acetaminophen;
• Patients who are known to be intolerant to all gout attack management regiments (participants must be able to tolerate at least one: Colchicine and/or Nsaids and/or Prednisone 0.5 mg/kg daily；
• Patients who have previously been treated with pegyluricase or other recombinant uricase, or who have been treated with other pegylated biological products;
• Participation in other clinical study with a drug intervention within 4 weeks before initiation of methotrexate or the drug was still in the elimination phase before screening (within 5 half-lives), whichever is older;
• Patients with chronic liver disease such as hepatitis, cirrhosis, alcoholic liver disease;
• Patients have unstable angina, severe arrhythmias requiring drug intervention, congestive heart failure (NYHA grade≥Ⅱ), uncontrolled hypertension (over 150/95 mmHg), poor glycemic control in diabetics ( HbA1c≥7%), acute stroke, Severe or chronic hemorrhagic digestive disease, pleural and abdominal effusion;
• A history of hypoxanthine-guanine phosphoribosyltransferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome;
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency or G6PD test values below the lower limit of normal;
• Estimated glomerular filtration rate (eGFR) ≤40 mL/min/1.73m2, or currently receiving dialysis, or end-stage renal disease (CKD4-5);
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the upper limit of normal value or albumin below the lower limit of normal value during screening (before methotrexate treatment);

Sponsors & Collaborators

• Shanghai Institute Of Biological Products: lead
• The First Affiliated Hospital of Bengbu Medical University: collaborator
• The First Affiliated Hospital of Henan University of Science and Technology: collaborator

Study Sites (1)

The First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, China

RECRUITING

MeSH Terms

Conditions

Gout

Interventions

Injections; Methotrexate

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)

Drug Administration Routes; Drug Therapy; Therapeutics; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Huan Zhou, Master

  Co., Ltd Shanghai Institute Of Biological Products

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dandan Chen, Master

CONTACT

86-021-62800991; ddchen.sh@sinopharm.com

Chaorong Xu, Master

CONTACT

86-021-62800991; xuchaorong@sinopharm.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: According to the sequence from low-dose group to high-dose group, there are 12 participants in each group, totaling 36 participants.

Study Record Dates

• First Submitted: February 28, 2024
• First Posted: March 7, 2024
• Study Start: March 3, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)