This double-blind, randomized, placebo-controlled study will assess the safety and pharmacokinetics of ZB002 in healthy participants and in participants with rheumatoid arthritis (RA). The study consists of 2 parts. Part A: Single Ascending Dose (SAD), which will include only healthy volunteers. Part B: Multiple Ascending Dose (MAD), will commence after completion of the SAD study and will include RA participants.

Part A (SAD): Up to approximately 48 healthy volunteers across 6 cohorts randomized to receive ZB002 or placebo as a single dose.

Part B (MAD): Up to approximately 24 participants with RA across 3 cohorts randomized to receive ZB002 or placebo as multiple doses.

Main Inclusion Criteria

Part A SAD (HV):

• Healthy male or female participants 18 to 55 years of age.
• Body weight ≥ 50 kg for male participants and ≥ 45 kg for female participants; body mass index of 18 to 35 kg/m^2 for both male and female participants.
• Considered in good health as determined by the Investigator.
• Female participants of child-bearing potential must agree to abstinence or use an effective form of contraception.
• Male participants must be surgically sterile or agree to use effective contraception.
• Willing and able to understand the characteristics and purposes of the study, including possible risks involved, and willing to comply with all the study requirements and provide written informed consent for the study.

Part B MAD (RA Participants):

• Male or female participants 18 to 70 years (inclusive) of age at Screening.
• Body mass index of ≥ 18.0 and ≤ 40.0 kg/m2.
• Diagnosis of RA and meeting the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria for RA ≥ 3 months before Screening.
• Use of methotrexate at 7.5 to 25 mg/week for ≥ 3 months, with stable dosing for ≥ 4 weeks, before randomization. Hydroxychloroquine/chloroquine and/or sulfasalazine are allowed if started ≥ 3 months before randomization and a stable dose is maintained after the Screening Visit.

Main Exclusion Criteria

Part A SAD (HV):

• Surgery within 4 weeks before Screening or planned surgery during the clinical study.
• Use of prescription medications, biological products, or other medicines within 2 weeks before Study Day 1 or 5 half-lives of the product, whichever is greater. Use of over-the-counter medications or vitamins/dietary supplements within 7 days of dosing unless considered by the Investigator to not pose a risk or impact the study results.
• Treatment with any investigational drug within 30 days or 5 half-lives, whichever is greater, before the first dose of the study drug, or currently enrolled in another clinical study.
• Clinically significant ECG abnormality.
• Positive for HIV infection, active hepatitis C, or hepatitis B.
• Positive for COVID-19 virus.
• Positive QuantiFERON®-TB Gold or T-SPOT® test for Mycobacterium tuberculosis.
• Bacteria, viruses, systemic fungi, parasites, or other opportunistic infections within 30 days before Study Day 1.
• Documented history of drug abuse in the previous 12 months before Screening, or positive for urine drug screen on Screening and/or Day -1.
• Donated blood (including component blood) or lost > 400 mL within 3 months before Screening or received a transfusion within 3 months of Screening.
• History of relevant allergies (including allergy to any murine or human-derived protein or immunoglobulin products, rubber or latex, or other allergies that in the opinion of the Investigator make inclusion in the study inappropriate).
• Average daily smoking > 10 cigarettes or cigarette equivalents per day within 6 months of Screening.
• Consume > 14 standard units of alcohol per week (1 standard unit is equivalent to approximately 360 mL of beer, 45 mL of spirits with 40% alcohol, or 150 mL of wine) or a positive alcohol breath test on Day -1.

Part B MAD (RA Participants):

• Inflammatory joint disease other than RA. Note: Current diagnosis of secondary Sjogren's Syndrome is permitted.
• Surgery within 4 weeks before Screening or planned surgery during the clinical study.
• History of any malignancy within 5 years, except for successfully treated nonmelanoma skin cancer or localized carcinoma in situ of the cervix.
• Documented history of drug abuse in the previous 12 months before Screening (Days -28 to -1), or positive for urine drug screen for nonprescribed drugs other than cannabinoid at Screening.
• Any condition considered by the investigator to make participation in the study inappropriate.
• Donated blood (including component blood) or lost > 400 mL within 1 month before Screening or received a transfusion within 3 months of Screening.
• After the Screening Visit, corticosteroid use > 10 mg/day (prednisone equivalent) or increase in dose
• Positive for HIV infection, active hepatitis C, or hepatitis B.
• Test positive for Mycobacterium tuberculosis.
• Bacterial, viral, systemic fungal, parasitic, or opportunistic infection not resolved at least 14 days before Study Day 1 or expected to be treated with antibiotics during the Treatment Period, or history of recurrent infections.
• Employees or related personnel of the study site, the sponsor, or contract research organization.