A Phase 2, Two-Part Study to Evaluate the Safety and Tolerability of GEn-1124 in Subjects With Acute Respiratory Distress Syndrome (ARDS)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 52
- 试验地点
- 22
- 主要终点
- To assess the safety and tolerability (SAEs and TEAEs) of GEn-1124
研究概览
简要总结
GEn1E-1124-002 is a two-part Phase 2 study to evaluate the safety and tolerability of GEn-1124 in subjects with ARDS. Treatment with IV infusion dosing as early as possible after ARDS diagnosis. Subjects will be given a second dose approximately 8 hours after the first dose and will continue with twice daily dosing (BID regimen) for 5 days.
详细描述
Randomized , double-blind, placebo controlled, dose escalation study to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of GEn1124.
GEn-1124 or placebo will be administered as a 2-hour IV infusion as early as possible after ARDS diagnosis. Participants will receive a second dose approximately 8 hours after the first and will continue BID for the remaining schedule (Days 2-5). Follow-up will be for a total of 60 days after the first dose or death (whichever comes first).
An independent Safety Review Committee (SRC) will be responsible for reviewing data throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
All subjects, investigators, and study personnel involved in the conduct of the study, including data management, will be blinded to treatment assignment with the exception of some designated personnel. The unblinded study personnel will not participate in study procedures or data analysis prior to unblinding of the study data to all study-related personnel.
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subject between the ages of 18 and 85 years old, inclusive.
- •Written informed consent .
- •Dosing as early as possible after first meeting ARDS 2023 Global definition.
- •Acceptable method of birth control.
排除标准
- •Subject, surrogate, or physician not committed, or eligible, to receive full supportive care measures.
- •Pregnant or breastfeeding
- •Currently incarcerated in a correctional institution or involuntarily committed to an inpatient mental health facility.
- •Active malignancy (other than non-melanoma skin cancer) requiring treatment with immunosuppressant drugs within the last 3 months or within the last 6 months if an anti-B cell antibody was received.
- •Any other irreversible disease or condition for which 6-month mortality is estimated to be >50%.
- •Moderate to severe liver failure.
- •Estimated glomerular filtration rate (eGFR) <10 mL/min/1.73 m2 or requiring dialysis at screening.
- •Subjects with known:
- •New York Heart Association Class IV heart disease; or
- •Acute Coronary Syndrome within the past 30 days (e.g., myocardial infarction, unstable angina) or dosing; or
- •Cardiac arrest within 30 days of dosing with sequelae likely to increase mortality.
- •Severe chronic respiratory disease with continuous home oxygen >2 liters per minute (LPM) or >28% (adjusted for altitude); and/or home noninvasive ventilation (except for the treatment of obstructive sleep apnea).
- •Poly-traumatic injury resulting in significant blood loss and/or likely to require major surgery within the study period, or subject condition that would interfere with study procedures.
- •History of any type of solid organ or cellular transplant.
- •Receiving immunosuppressive therapy for solid organ or hematopoietic cancer, transplant anti-rejection medication, and/or other chronic conditions.
- •Moribund subject not expected to survive 24 hours.
- •Do not resuscitate (DNR) status.
- •World Health Organization (WHO) functional class III or IV pulmonary hypertension.
- •Subject has been on mechanical ventilation for more than 7 days at time of dosing.
- •Burn victims currently undergoing treatment for >40% total body surface area (TBSA) involvement or for known airway inhalation injury.
- •Neuromuscular disease that could impact ability to wean from mechanical ventilation.
- •History of tuberculosis (TB); undergoing treatment for latent TB infection (LTBI); untreated LTBI (as determined by documented results within 3 months of Screening of a positive TB test).
- •Active Hepatitis B, positive Hepatitis C (and has not completed antiviral treatment), or positive human immunodeficiency (HIV) screen.
- •Use of any investigational drug or device within last 30 days of dosing or 5 half-lives, whichever is longer.
- •Any other medical, psychiatric, or social condition that, in the opinion of the investigator, is likely to unfavorably alter the risk-benefit of subject participation, to interfere with protocol compliance, or to confound safety.
研究组 & 干预措施
Part 1 Cohort 1: GEn-1124
Subjects in cohort 1 will receive low dose GEn-1124 BID intravenous 5 days.
干预措施: GEn-1124 (Drug)
Part 1 Cohort 2: GEn-1124
Subjects in cohort 2 will receive high dose GEn-1124 BID intravenous for 5 days.
干预措施: GEn-1124 (Drug)
Placebo
Subjects randomized to placebo will receive a placebo in a matching dosing regimen (Placebo BID intravenous for 5 days).
干预措施: Placebo (Drug)
Part 2: GEn-1124
Depending on the analysis of part 1, subjects in part 2 will receive GEn-1124 BID intravenous for 5 days.
干预措施: GEn-1124 (Drug)
结局指标
主要结局
To assess the safety and tolerability (SAEs and TEAEs) of GEn-1124
时间窗: Through study completion, Day 60
* Incidence (frequency over time) of serious adverse events (SAEs) unexpected in ARDS patients. * Incidence (frequency over time) of treatment-emergent adverse events (TEAE).
次要结局
未报告次要终点