Role of L-Arginine Supplementation in the Treatment of Rheumatoid Arthritis

Inclusion Criteria: In order to be eligible for inclusion in this study, subjects must meet all of thefollowing criteria:

• Chinese RA patients who are between 18 and 45 years old (inclusive) when signing theconsent form, with a body mass index between 19 and 29 kg/m2 (inclusive), and weighbetween 60 and 90 kg.

• The subject must be diagnosed with RA, and the judgment standard meets the 2010American College of Rheumatology (ACR)/European Alliance Against Rheumatism (EULAR) RAclassification standard;

• Active RA is defined as having ≥ 6 swollen joints and ≥ 6 tender joints at screeningand baseline (based on 66/68 joints, excluding distal interphalangeal joints), and atleast one of the following conditions occurs during screening: ESR ≥ 28 mm/hr, orserum CRP> 10 mg/L;

• Positive rheumatoid factor or anti-cyclic citrulline peptide (CCP) during screening;

• Before using the study drug, the subject must have used MTX continuously for ≥ 12weeks and have been stable for at least 8 weeks.

• 10-15mg/week dose and willing to use a stable dose throughout the study;

• Patients with moderate to severe disease activity after the current treatment ofDMARDs, DAS28-ESR/CRP>3.2;

• Subjects taking oral corticosteroids (≤ 10 mg of prednisone or equivalent) should usea stable dose for ≥ 4 weeks before screening;

• If subjects are taking non-steroidal anti-inflammatory drugs (NSAIDs) orlow-efficiency analgesics, such as tramadol, neuronal cell compounds, they must use astable dose for ≥ 2 weeks before screening.

• Considered as eligible subjects based on the following tuberculosis screeningcriteria:

1. The subject has no history of latent or active tuberculosis before screening,

2. No signs or symptoms of active tuberculosis in the history and/or physicalexamination,

3. Have not had close contact with patients with active tuberculosis recently,

4. One chest radiograph (including anteroposterior and lateral views) taken withinthree months before the administration of the study drug, and qualifiedradiologists have confirmed that there are no active tuberculosis foci or oldinactivated tuberculosis foci.

• Non-smokers, or agree to smoke no more than 10 cigarettes or no more than 2 cigars perday during the entire study period. Note: According to the rules and regulations ofthe research center, smoking may be prohibited during hospitalization;

• Agree to abstain from alcohol within 48 hours before the administration of the studydrug and during the study hospitalization, and agree to drink no more than 10g ofalcohol per day during the rest of the study;

• Agree to limit caffeine intake, with a daily limit of five cups of tea, or three cupsof coffee or six cans of cola. Do not take caffeine within 4 hours before receivingthe electrocardiogram;

• Agree to fully use birth control measures to prevent pregnancy (such as birth controlpills, uterine contraceptive devices, or protective measures using spermicides) for atleast six months after receiving study drug treatment;

• Except for taking acetaminophen and previously taken multivitamins at the recommendeddose, as well as the drugs approved by the investigator and medical monitor, thesubject agreed to not use prescription drugs for 14 days before receiving the studydrug treatment until the end of the study , Over-the-counter medicines, herbalmedicines, proprietary Chinese medicines or "natural" medicines;

• Demonstrate a clear understanding of the research and sign an informed consent (ICF);

• Personal willingness and ability to comply with the study follow-up schedule and otherrequirements of the study protocol.

Exclusion Criteria: Subjects who meet any of the following criteria should not be selected for this study:

• RA patients combined with hypotension.

• RA patients combined with renal tubular acidosis and electrolyte imbalance.

• RA patients with significant gastrointestinal symptoms.

• According to the judgment of the main investigator, the subject is in a latentphysical or psycho-medical state and will not be able to complete the study.

• Have had major surgery or traumatic surgery within 12 weeks before screening.

• Have received an organ transplant (except for corneal transplantation for more thanthree months before administration).

• Donated blood within 56 days before screening (the blood donation volume is not lessthan 500 mL).

• Currently suffering from malignant tumors or a history of malignant tumors.

• A history of known lymphoproliferative diseases, including lymphoma or possible signsand symptoms of lymphoproliferative diseases, such as lymphadenopathy and/orsplenomegaly.

• Have a recent history of alcohol or drug abuse (within the previous 6 months).

• Positive urine toxicology screening for drugs of abuse include: cocaine, cannabidiol,phencyclidine, amphetamine, methamphetamine, benzodiazepines, barbiturates, opioids,and C Oxyphene, methaqualone, methadone and tricyclic antidepressants.

• When admitted to the research center before the study drug was administered, the urinealcohol screening or breath alcohol test results were positive.

• Have a history of latent or active granulomatous infection before screening, includinghistoplasmosis or coccidioidomycosis.

• Have a history of known or suspected intolerance or hypersensitivity to any biologicaldrug treatment.

• Chest x-ray pictures taken within 3 months before the first administration of thestudy drug showed abnormalities suggesting malignant tumors or current activeinfections (including TB).

• Have nontuberculous mycobacteria or opportunistic infections (such as cytomegalovirus,pneumocystis disease, aspergillosis) within 6 months before screening.

• Have or have had a serious infection (such as sepsis, pneumonia, or pyelonephritis) orwere hospitalized for infection or received fourth-generation antibiotic treatmentwithin 2 months before screening.

• A history of chronic or recurrent infectious diseases, including but not limited tothe following diseases: chronic kidney infection, chronic chest infection (forexample, bronchiectasis), recurrent urinary tract infection (recurrent pyelonephritisor chronic non-dilated bladder) Inflammation), or open, draining or infectious skinwounds or ulcers.

• Serum was positive for HIV-1 or HIV-2, hepatitis B virus (HBV) or hepatitis C virus (HCV) during screening.

• Syphilis (Treponema pallidum) test (qualitative test) was positive at screening.

• The staff of the main researcher or research center and directly participate in theresearch or other research of the main researcher or research center, including thestaff or the family members of the main researcher.