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

Lifordi Immunotherapeutics, Inc.7 个研究点分布在 5 个国家目标入组 176 人开始时间: 2025年10月6日最近更新: 2026年7月28日

适应症

干预措施

试验速览

阶段: 1 期
状态: 招募中
发起方
入组人数: 176
试验地点: 7
主要终点: Incidence of Adverse Events (AEs)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Treatment
盲法: Triple (Participant, Care Provider, Investigator)

入排标准

年龄范围: 18 Years 至 75 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 是

入选标准

•for Healthy Participants:
•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.

排除标准

•for Healthy Participants:
•Participants with any current or previous illness that, in the opinion of the investigator, might confound the results of the study or pose an additional, unacceptable risk to the participant or that could prevent, limit, or confound the protocol specified assessments or study results' interpretation.
•Recent serious or ongoing infection
•Known/suspected primary immunodeficiency
•Receipt of injected or systemic glucocorticoids within 6 weeks prior to screening
•Use of prohibited medications
•Any of the following lab abnormalities:
•White blood cell (WBC) count <3.0 x 109/L
•Absolute neutrophil count (ANC) <2.0 x 109/L
•Hemoglobin (Hgb) <12.5 g/dL for males and <11.5 g/dL for females
•Platelet count <140 x 109/L
•Alanine transaminase (ALT) ≥1.2x upper limit of normal (ULN)
•Total bilirubin ≥1.2x ULN (except if Gilbert's disease is suspected etiology)
•Estimated glomerular filtration rate (eGFR) <80 mL/min/1.73m2 based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI 2021) formula.
•International normalized ratio (INR) ≥1.2 × ULN
•Glycated hemoglobin (HbA1c) >6%
•Positive urine cotinine test (Day -1 only), alcohol breath test or urine drug screen for substances of abuse. Positive tetrahydrocannabinol (THC) is not exclusionary.
•A Screening thyroid stimulating hormone (TSH) level that is <0.9 × lower limit normal (LLN) or ≥1.2 × ULN
•Cortisol level <1.0 × LLN (Collected in the AM at the Baseline Visit)
•Inclusion Criteria for RA Participants:
•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.
•Exclusion Criteria for RA Participants:
•Clinical evidence of significant unstable or uncontrolled acute or chronic diseases (e.g., cardiac [including congestive heart failure, angina, or history of myocardial infarction], pulmonary [including chronic obstructive pulmonary disease, asthma requiring systemic GC therapy, pulmonary hypertension, or pulmonary fibrosis], hematologic, gastrointestinal, hepatic, renal, neurological, psychiatric, dermatologic, musculoskeletal, or infectious diseases) that, in the opinion of the Investigator or Sponsor, constitutes an inappropriate risk or contraindication for participation in study or that could interfere with study objectives, conduct, or evaluation
•Any other autoimmune or autoinflammatory disorder, which in the opinion of Investigator/Sponsor would constitute an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation.
•Recent serious or ongoing infection, or risk for serious infection, or acute or chronic infection
•Known seropositivity for or active infection by HIV or strongyloides (if at risk of exposure (e.g., travel from/reside in endemic area))
•Active or latent TB infection, as suggested by a positive chest radiograph OR positive/indeterminate QFT-TB Gold Plus or T-SPOT within the 12 weeks prior to Screening or a positive Screening CXR or QFT test. Indeterminate screening QFT tests are also exclusionary but may be repeated once and will be considered positive if retest results are positive or indeterminate/borderline.
•Clinically significant abnormalities on ECG per the Investigator or Sponsor or any of the following mean ECG parameters on screening/baseline (triplicate) ECG:
•HR <40 or >100 beats per minute
•QTcF (Fridericia corrected QT) interval >450 ms (males) or >470 ms (females)
•QRS interval >120 ms
•PR interval >220 ms
•Use or anticipated use of medications for the timeframes specified below:
•Unstable use of any herbal medicines (e.g., St. John's wort) and supplements within 4 weeks prior to Screening through Baseline or anticipated changes in use during study.
•Systemic or local (e.g., topical, oral, ophthalmic) corticosteroid (CS) use within 6 weeks prior to randomization or anticipated use during the study (other than as study intervention).
•Any intra-articular injection within 4 weeks prior to Screening through Baseline or anticipated use during the study.
•Use of cyclophosphamide, chlorambucil, leflunomide for <6 months or cyclosporine, mycophenolic acid, azathioprine, tacrolimus, or gold <8 weeks prior to Screening through Baseline or anticipated use during the study.
•Receipt of rituximab or any other cell depleting biologic therapy within 1 year of Screening through Baseline or anticipated use during the study.
•Use of any other commercial injectable biologic (including those for other non- arthritic conditions such as asthma, osteoporosis, lipids, atopic dermatitis) within 12 weeks or 5 half-lives (whichever is longer) prior to Screening through Baseline, or anticipated use during the study.
•Use of any other oral DMARD, including JAK-inhibitors, within 12 weeks prior to Screening through Baseline or anticipated used during the study. MTX or HCQ use is permitted as specified in the Inclusion Criteria
•Use of >1 systemic biologic therapy for the treatment of RA prior to Screening or Baseline. For those participants that have used no more than one systemic biologic therapy, the systemic biologic therapy must have been discontinued at least 12 weeks or 5 half-lives (whichever is longer) prior to Screening with no use through Baseline or anticipated use during the study.
•Receiving or has received any investigational drug (or is currently using an investigational device) within 30 days or 5 half-lives (whichever is longer), prior to Screening.
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研究组 & 干预措施

Part 1: SAD in HP

Experimental

Three planned cohorts (SAD HP Cohorts 1 to 3) and 3 optional cohorts (SAD HP Cohorts 4 to-6) of 11 participants each will receive a single SC dose of LFD-200, a single SC dose of matching saline placebo, or a single oral dose of open label 10 mg prednisone. Within each cohort, 6 participants will be randomly assigned to receive LFD-200, 2 participants will receive saline placebo, and 3 will receive prednisone.

干预措施: LFD-200 (Drug)

Part 1: SAD in HP

Experimental

干预措施: Placebo (Other)

Part 1: MAD in HP

Experimental

Two planned cohorts (MAD HP Cohorts 1 and 2) of 8 HPs each (16 total) will be randomly assigned to receive 4 weekly SC doses of LFD-200 (6 participants) or saline placebo (2 participants) over a duration of 22 days.

干预措施: Placebo (Other)

Part 2: MAD in RA

Experimental

Two planned cohorts (MAD RA Cohorts 1 and 2) of 14 RA participants each (28 total) will be randomly assigned to receive either up to 13 weekly SC doses of LFD-200 over 85 days with a daily prednisone placebo tablet (LFD-200 arm; 8 participants), or up to 13 weekly SC doses of saline placebo over 85 days with daily prednisone placebo tablet (placebo arm; 3 participants), or up to 13 weekly SC doses of saline placebo over 85 days with a daily dose of oral prednisone (prednisone arm; 3 participants)

干预措施: LFD-200 (Drug)

Part 2: MAD in RA

Experimental

干预措施: Placebo (Other)

Part 1: SAD in HP

Experimental

干预措施: Oral Prednisone (Drug)

Part 1: MAD in HP

Experimental

干预措施: LFD-200 (Drug)

Part 2: MAD in RA

Experimental

干预措施: Oral Prednisone (Drug)