Phase II/III Study of AR882 Capsules Compared to Febuxostat Tablets in Patients with Primary Gout and Hyperuricemia

A Multicenter, Randomized, Double-Blind, Parallel-Controlled Phase II/III Study to Evaluate the Efficacy and Safety of AR882 Capsules Compared to Febuxostat Tablets in Patients with Primary Gout and Hyperuricemia

The goal of this clinical trial is to evaluate the efficacy and safety of AR882 Capsules in patients with primary gout and hyperuricemia. The main questions it aims to answer are:

What is the efficacy of AR882 Capsules in reducing serum uric acid levels in patients with primary gout and hyperuricemia?

Researchers will compare AR882 Capsules with Febuxostat Tablets to see :

Phase II: To explore the efficacy of AR882 Capsules in patients with primary gout and hyperuricemia, aiming to determine the dosing regimen for the Phase III study Phase III: To evaluate the efficacy of AR882 Capsules in patients with primary gout and hyperuricemia.

Participants will:

Be randomly assigned to receive either AR882 Capsules or Febuxostat Tablets. Undergo regular assessments of serum uric acid levels. Report any adverse events or side effects experienced during the study.

Study Overview

• Status: Active, not recruiting
• Conditions: Hyperuricemia; Primary Gout
• Intervention / Treatment: Drug: Febuxostat 20MG Placebo; Drug: AR882 25MG; Drug: AR882 12.5MG; Drug: Febuxostat 40MG Placebo; Drug: Febuxostat 20MG Tablets; Drug: AR882 25MG Placebo; Drug: AR882 12.5MG Placebo; Drug: Febuxostat 40MG Tablets

• Study Type: Interventional
• Enrollment (Estimated): 636
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital, Chinese Academy of Medical Science

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female patients ≥ 18 and ≤ 75 years of age at the time of signing the informed consent form (ICF)；
• History of gout according to the 2015 American College Rheumatology/European League Against Rheumatism (ACR/EULAR) Gout Classification Criteria，with serum urate (sUA) levels ≥480μmol/L；
• Body mass index (BMI) must be within the range of ≥ 18 to ≤ 35 kg/m2；
• Participants with childbearing potential must agree to use medically accepted effective contraception during the study period and for 3 months after the last dose
• Willing to participate in the study and sign the informed consent form.

Exclusion Criteria:

• Known or suspected allergy to the study drug or its components, or previous intolerance or contraindications to febuxostat；
• HbA1c ≥8% within 2 weeks prior to randomization；
• Any of the following laboratory test results within 2 weeks prior to randomization：WBC<3.0×109/L，Hb<90g/L，PLT<80×109/L，ASTorALT>1.5×ULN，TBIL>1.5×ULN，Scr>1.5×ULN，eGFR<60mL/min/1.73m2；
• Use of any other uric acid-lowering drugs or concomitant medications affecting uric acid levels (including but not limited to losartan, calcium channel blockers, fenofibrate, atorvastatin, α-glucosidase inhibitors, insulin sensitizers, DPP4 inhibitors, SGLT2 inhibitors, metformin) within 2 weeks prior to randomization, except for stable dose usage；
• Use of aspirin >100 mg/day or unstable dosage within 2 weeks prior to randomization；
• Use of any diuretics within 2 weeks prior to randomization；
• Use of a strong or moderate CYP2C9 inhibitor or BCRP substrate drugs (see Appendix 2) within 2 weeks prior to randomization；
• Secondary hyperuricemia due to tumors, chronic kidney disease, hematological diseases, medications, or hereditary hyperuricemia；
• Presence of unresolved gout attacks within 2 weeks prior to randomization；
• Imaging or clinical manifestations (e.g., hematuria, back pain) of kidney stones or urolithiasis within 2 weeks prior to randomization；
• Other joint lesions that may confound gouty arthritis, such as rheumatoid arthritis, septic arthritis, traumatic arthritis, psoriatic arthritis, pseudogout, systemic lupus erythematosus, or joint diseases caused by chemotherapy, radiotherapy, chronic lead poisoning, acute obstructive nephropathy, etc.;
• Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin and resected cervical intraepithelial neoplasia that has been successfully treated；
• Severe cardiovascular or cerebrovascular diseases, such as New York Heart Association (NYHA) Class III-IV congestive heart failure, uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg), QTcF interval (Fridericia's formula) prolongation (male >450 ms, female >470 ms), myocardial infarction, acute stroke, uncontrolled arrhythmia, or unstable angina within 12 months prior to screening；
• Unable to swallow oral medications or have gastrointestinal diseases that may interfere with drug absorption, or have active gastric or duodenal ulcers within 3 months prior to screening；
• Systemic diseases requiring immunosuppressive therapy, or vaccination within 2 weeks prior to randomization；
• Other severe or uncontrolled diseases；
• History of xanthinuria；
• Poor compliance (e.g., alcoholism, drug abuse) that may affect the safety and efficacy evaluation of the study drug, as judged by the investigator；
• Pregnant or breastfeeding women；
• Any acute inflammation or clinically significant active infection；
• Active hepatitis B (HBsAg positive and HBV-DNA >1000 IU/mL), or positive for serum HCV antibodies, HIV antibodies, or syphilis antibodies；
• Previous kidney removal and/or kidney transplantation；
• Major surgery within 3 months prior to randomization, or planned major surgery during the study；
• Blood donation (or blood loss) ≥400 mL or blood transfusion within 3 months prior to randomization；
• Participation in another drug clinical trial within 3 months prior to screening or within 5 half-lives of the investigational product (whichever is longer), or participation in a medical device clinical trial within 3 months prior to screening；
• Any other condition deemed unsuitable for study participation by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AR882 50MG; Titrated from 12.5 mg to 25 mg (2 weeks each), then 50 mg for 4 weeks, with matching Febuxostat placebo.	Drug: Febuxostat 20MG Placebo; Febuxostat 20MG Placebo; Drug: AR882 25MG; AR882 25 MG Capsules; Drug: AR882 12.5MG; AR882 12.5 MG Capsules; Drug: Febuxostat 40MG Placebo; Febuxostat 40MG Placebo
Active Comparator: Febuxostat 40MG; Titrated from 20 mg (4 weeks) to 40 mg (4 weeks) Febuxostat, with matching AR882 placebo.	Drug: Febuxostat 20MG Tablets; Febuxostat 20MG Tablets; Drug: AR882 25MG Placebo; AR882 25MG Placebo; Drug: AR882 12.5MG Placebo; AR882 12.5MG Placebo; Drug: Febuxostat 40MG Tablets; Febuxostat 40MG Tablets
Experimental: AR882 75MG; Titrated from 25 mg to 50 mg (2 weeks each), then 75 mg for 4 weeks, with matching Febuxostat placebo.	Drug: Febuxostat 20MG Placebo; Febuxostat 20MG Placebo; Drug: AR882 25MG; AR882 25 MG Capsules; Drug: Febuxostat 40MG Placebo; Febuxostat 40MG Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The percentage of participants with serum uric acid <360 μmol/L	8 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The percentage of participants with serum uric acid <300, 240 μmol/L	8 Weeks
The percentage of participants with serum uric acid <360, 300, 240 μmol/L	2, 4, and 6 Weeks
The absolute change in serum uric acid levels from baseline	2, 4, 6, and 8 Weeks
The percentage change in serum uric acid levels from baseline	2, 4, 6, and 8 Weeks
Serum uric acid levels	2, 4, 6, and 8 Weeks
Adverse events	8 Weeks

Collaborators and Investigators

• Sponsor: Guangzhou Ruianbo Pharmaceutical Technology Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: September 17, 2024
• First Submitted That Met QC Criteria: September 17, 2024
• First Posted (Estimated): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 17, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Gout; Hyperuricemia; URAT1; ULT
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Metabolism, Inborn Errors; Crystal Arthropathies; Purine-Pyrimidine Metabolism, Inborn Errors; Hyperuricemia; Gout; Arthritis, Gouty; Antirheumatic Agents; Gout Suppressants; Febuxostat
• Other Study ID Numbers: APRAB-H001-P301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No