A Phase 1a/1b, Randomized, Double-Blind, Placebo- and Active-Controlled, Single and Multiple Ascending Dose Study Evaluating the Comparative Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LFD-200 in Adult Participants Who Are Healthy or Have Moderate to Severe Rheumatoid Arthritis
This is a double-blind, randomized, placebo- and active-controlled study investigating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of subcutaneous (SC) doses of LFD-200. The study design includes: a single ascending dose (SAD) study in up to 66 adult healthy participants (HPs) to investigate the effects of a single SC dose, with a 30-day follow-up; a multiple ascending dose (MAD) study in up to 40 HPs to assess up to 4 weekly SC doses, with a 30-day follow-up after the last dose; and a MAD study in up to 70 participants with moderate to severe rheumatoid arthritis (RA) to evaluate up to 13 weekly SC doses, with a 30-day follow-up after the last dose.
• Age 18-55
• BMI - 18-32
• Participants must be deemed by the Investigator to be generally healthy individuals based on a medical evaluation that includes a physical examination, medical history, vital signs, and the results from clinical labs and other safety assessments collected during the Screening period.
• Adults of age 18 to 75 years, inclusive, at the time of signing the ICF.
• BMI within the range of 18.0- to 35.0 kg/m² (inclusive).
• Has RA for ≥6 months.
• Positive rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA) test at Screening (low or high positive acceptable).
• A high-sensitivity C-reactive protein (hsCRP) level at Screening must be \>ULN.
• Has active RA disease defined as follows:
‣ Disease Activity Score of 28 joints-CRP (DAS28-CRP) \>3.2 at Screening and Baseline
⁃ Has ≥4 swollen and ≥4 tender joints on a 28-joint count at Screening and Baseline
• On MTX orally or subcutaneously for at least 12 weeks prior to Screening. Dose of MTX (including route of administration) must have been stable at 15 to 25 mg weekly (or 10 to15mg in case of documented intolerance) for ≥ 12weeks at Randomization with plans to continue it at the same dose and route of administration for the duration of the study.