A Study to Evaluate the Efficacy,Safety,Tolerability,Pharmacokinetics,and Immunogenicty of Plonmarlimab in Subjects With Acute Gouty Arthritis

Official title

A Multicenter, Randomized, Double-Blind, Double-Dummy, Active-Controlled Phase II Clinical Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Punarlimab in Subjects With Acute Gouty Arthritis

Overview

This is a multi center,randomized,double-blind,double-dummy,active-controlled study,and planned enrollment of 120-170 subjects,an interim analysis will be conducted after first 60 subjects complete the 72 -hour pain Visual Analogue Scale(VAS) assessment following their initial dose.Based on the analysis result，the sample size may be adjusted, and 1or 2 group(s）of the investigational drug will be selected to continue enrollment along with the active comparator group.The goal is to evaluate the efficacy of plonmarlimab in subjects with acute gouty arthristis.

Interventions

• Drug Plonmarlimab
  single dose, intravenous infusion
• Drug Compound betamethasone
  single dose, intramuscular injection
• Drug Plonmarlimab placebo
  single dose, intravenous infusion
• Drug Compound betamethasone placebo
  single dose, intramuscular injection

Primary outcome measures

• Visual Analogue Scale(VAS) score [Time frame: 72 hours after the initial dose.]

Eligibility criteria

Inclusion criteria

• Subjects aged ≥18 years, regardless of gender.
• Subjects are willing to participate in this study and voluntarily sign the informed consent form.
• Meet the 2015 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) gout classification criteria.
• Experienced ≥3 episodes of acute gout flare within the 12 months prior to baseline (determination of an acute gout flare based on patient history, referral records, etc., will be made by the investigator).
• Subjects have experienced an acute gout flare within 5 days prior to administration of the investigational product (determination of an acute gout flare based on patient history, referral records, etc., will be made by the investigator).
• Contraindicated, intolerant, or inadequately responsive to colchicine and/or non-steroidal anti-inflammatory drugs (NSAIDs) (determination based on patient history, referral records, etc., will be made by the investigator).
• Baseline pain intensity assessment in the most severely affected joint by the subject using a 0-100 mm Visual Analogue Scale (VAS) is ≥50 mm.
• Subjects may or may not be receiving urate-lowering therapy. If planning to continue urate-lowering therapy during the study, it must have been at a stable dose for ≥2 weeks prior to baseline.
• Subjects (including their partners) have no pregnancy plans from the screening period until 90 days after dosing and voluntarily agree to use effective contraception.

Exclusion criteria

• Secondary gout caused by various etiologies (e.g., gout induced by chemotherapy, judged by the investigator based on the subject's medical history, referral records, etc.).
• History of hypersensitivity to any component of the investigational product or to similar biological agents.
• Contraindication to compound betamethasone therapy.
• Presence of other rheumatic diseases besides gout that may interfere with interpretation of results, including but not limited to rheumatoid arthritis, infectious/suppurative arthritis, traumatic arthritis, etc.
• Pulmonary diseases including but not limited to asthma, chronic obstructive pulmonary disease, interstitial lung disease, pulmonary alveolar proteinosis, pulmonary granulomatosis, etc., or any underlying pulmonary disease that significantly impairs pulmonary function as assessed by the investigator, making the subject unsuitable for this clinical study.
• Cardiovascular diseases: history of acute myocardial infarction, unstable angina, severe arrhythmia (multifrequent premature ventricular contractions, ventricular tachycardia, ventricular fibrillation) within the past 6 months; New York Heart Association (NYHA) functional Class III-IV (see Appendix 4). Presence of long QT syndrome or QTc interval > 450 msec (male) or > 470 msec (female) during screening.
• History of malignancy within the past 5 years (regardless of treatment), except for successfully treated basal cell or squamous cell carcinoma of the skin.
• Other diseases: subjects with a past and/or current clinically significant, unstable, or uncontrolled acute or chronic disease unrelated to gout (e.g., acute pneumonia, pulmonary hypertension, diabetic ketoacidosis, acute pancreatitis, etc.), or scheduled medical/surgical procedures; or any condition that places the subject at undue risk or impairs the ability to participate voluntarily.
• Infections: presence of any known acute, chronic, or recurrent active infection during screening (e.g., tuberculosis, syphilis, HIV, HBV, HCV, Pneumocystis jirovecii, CMV, HSV, VZV, atypical mycobacteria, Histoplasma capsulatum, Salmonella infection, genital herpes, osteomyelitis, urinary tract infection, etc.).
• Abnormal hepatic and renal function: aspartate aminotransferase (AST), alanine aminotransferase (ALT), or gamma-glutamyl transferase (GGT) > 2 × upper limit of normal (ULN); alkaline phosphatase (ALP) or total bilirubin (TBIL) > 1.5 × ULN; creatinine (Cr) or blood urea nitrogen (BUN) > 1.5 × ULN; or eGFR ≤ 60 mL/min/1.73 m² prior to screening (calculated using the MDRD formula, see Appendix 9).
• Hematological diseases or abnormal routine blood tests: subjects with a past or current hematological disease including but not limited to myelofibrosis, aplastic anemia, leukemia, lymphoma, etc.; hemoglobin < 90 g/L, platelet count < 80×10⁹/L, white blood cell or neutrophil count below the lower limit of normal with clinically significant abnormality judged by the investigator.
• Planned surgery or any other medical history (e.g., recent sepsis), laboratory abnormality, or other condition judged by the investigator to render the subject ineligible for this study.
• History of organ transplantation.
• Pregnant or lactating female subjects.
• Participation in any interventional clinical trial (including investigational vaccines) or use of an invasive investigational medical device within 3 months prior to enrollment, or current enrollment in another interventional study.
• Administration of live (attenuated) vaccine within 30 days prior to screening. Inability to receive intramuscular injection (e.g., subjects on anticoagulants, thrombocytopenia, known bleeding disorders such as idiopathic thrombocytopenic purpura).
• Drug abuse detected by urine drug screening, including morphine, ketamine, tetrahydrocannabinol, methamphetamine, MDMA, cocaine.
• Alcohol abuse within 3 months prior to screening, defined as alcohol consumption > 14 units per week (1 unit = 17.5 mL or 14 g pure alcohol; 1 unit ≈ 35 mL of 50% spirits or 350 mL of 5% beer), or unwillingness to abstain from alcohol or alcohol-containing products during the trial.
• Any other condition deemed by the investigator to render the subject unsuitable for this clinical study, including any condition that may increase study-related risk, interfere with evaluation of the investigational product, or confound interpretation of study results.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Renji Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai

Identifiers

NCT: NCT07453004 · THZ0103-203

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗