Open-label, Pharmacokinetic, Pharmacodynamic, Ascending Dose Safety lead-in Followed by a Single-center, Placebo-controlled, Double-blind, Adaptive, Safety and Efficacy, Pilot Study of Trans Sodium Crocetinate (TSC) in SARS-CoV-2 Infected Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
研究概览
简要总结
This study will assess the safety and efficacy of TSC as a treatment for participants who are infected with SARS-CoV-2 (COVID-19).
详细描述
This trial has two phases. The first phase is an open-label, pharmacokinetic, pharmacodynamic, ascending dose, safety and tolerability lead-in. The second phase is a single-center, randomized, placebo-controlled, double-blind, adaptive, safety and efficacy, pilot.
The lead-in phase will study 4 doses of TSC and enroll 24 participants. Each TSC dose will be administered as an IV bolus injection to 6 unique participants per dose level administered four times per day (every 6 hours) for 5 days. Participants will be assigned in groups of 3, and a Safety Monitoring Committee (SMC) will review Dose Limiting Toxicities (DLTs) after each group of 3 participants. The first group of 3 participants will receive TSC at a dose of 0.25 mg/kg. If there are no DLTs, 3 additional subjects will be studied at 0.25 mg/kg. If there are 0 or 1 DLT among the 6 participants studied at 0.25mg/kg, 3 additional participants will be studied at the next higher dose, 0.5 mg/kg. If there are no DLTs an additional 3 participants will be studied at 0.5 mg/kg. If there are 0 or 1 DLTs among the 6 subjects studied at 0.5 mg/kg, 3 additional participants will be studied at the next higher dose, 1.0 mg/kg. The study will continue in this fashion seeking an observed toxicity rate that is < 0.33 among 6 participants at any one dose level, or TSC at 1.5 mg/kg proves to be safe and tolerable.
As participants complete the initial 5 days of treatment they will continue at their assigned TSC dose four times per day (every 6 hours) for up to 15 days. Participants will be assigned to dose levels in ascending order. The dose range is as follows.
- 0.25 mg/kg TSC + Standard of Care
- 0.50 mg/kg TSC + Standard of Care
- 1.00 mg/kg TSC + Standard of Care
- 1.50 mg/kg TSC + Standard of Care
At the completion of the lead-in the Safety Monitoring Committee (SMC) will examine the resultant safety and blood oxygenation (S:F) data for all participants and determine the optimum, safe and tolerable dose of TSC for use in the pilot study.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Lead-in: no masking. Randomized pilot: The participants, care providers, investigators, and outcomes assessors are masked. The pharmacist, unblinded clinical research associate, and unblinded study drug administrator are not masked.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hospitalized subjects with confirmed SARS-CoV-2 infection and hypoxemia, defined as SpO2 < 94% on room air or requiring supplemental oxygen
- •Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen < 72 hours prior to enrollment.
- •WHO ordinal scale score of 3, 4 or 5 at baseline
- •Male or non-pregnant female adult ≥18 years of age at time of enrolment.
- •Subject (or legally authorized representative (LAR)) provides written informed consent prior to initiation of any study procedures.
- •Understands and agrees to comply with planned study procedures.
- •Illness of any duration
- •Women of childbearing potential must have a negative blood pregnancy test at the screening/baseline visit (Day 1) and agree to use a double method of birth control through 30 days after the last dose of study drug.
排除标准
- •Intubated and mechanically ventilated at baseline
- •Receiving extracorporeal membrane oxygenation (ECMO) at baseline
- •Severe organ dysfunction (SOFA score > 10)
- •Patient or LAR unable to provide written informed consent
- •ALT/AST > 3 times the upper limit of normal or serum bilirubin > 1.5 times the upper limit of normal
- •Estimated glomerular filtration rate (eGFR) by Modification of Diet in Renal Disease (MDRD) formula < 30 mL/min/1.73 m^2 or on dialysis
- •Pregnancy or breast feeding.
- •Anticipated transfer to another hospital which is not a study site within 72 hours.
- •Allergy to any study medication
研究组 & 干预措施
Lead-in 0.25 mg/kg
0.25 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days
干预措施: Trans Sodium Crocetinate (Drug)
Lead-in 0.50 mg/kg
0.50 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days
干预措施: Trans Sodium Crocetinate (Drug)
Lead-in 1.0 mg/kg
1.0 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days
干预措施: Trans Sodium Crocetinate (Drug)
Lead-in 1.5 mg/kg
1.5 mg/kg TSC, administered via IV bolus every 6 hours for up to 15 days
干预措施: Trans Sodium Crocetinate (Drug)
Randomized Active TSC
TSC, at the optimum safe and tolerable dose determined in the lead-in phase, administered via IV bolus every 6 hours for up to 15 days
干预措施: Trans Sodium Crocetinate (Drug)
Randomized Placebo
Normal Saline, in an equivalent volume by participant body weight, administered via IV bolus every 6 hours for up to 15 days
干预措施: Normal saline (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
时间窗: Up to 70 days post-study drug administration
Lead-in phase: Overall summary of subjects with TEAEs
Time to Recovery Through Day 28
时间窗: 28 days
Lead-in phase: Time to achieve (and maintain through Day 28) a World Health Organization (WHO) ordinal COVID-19 severity scale score of 1, 2 or 3 with a minimum 1-point improvement from baseline. The scale assesses clinical status and the range is 0-8, as follows: 0. Uninfected - No clinical or virological evidence of infection 1. Ambulatory - No limitation of activities 2. Ambulatory - Limitation of activities 3. Hospitalized, Mild Disease - Hospitalized, no oxygen therapy 4. Hospitalized, Mild Disease - Oxygen by mask or nasal prongs 5. Hospitalized Severe Disease - Non-invasive ventilation or high-low oxygen 6. Hospitalized Severe Disease - Intubation and mechanical ventilation 7. Hospitalized Severe Disease - Ventilation + additional organ support (pressors, Renal Replacement Therapy (RRT), Extracorporeal Membrane Oxygenation (ECMO) 8. Dead - Death
次要结局
- Hospital Length of Stay(28 days)
- Oxygenation - Time to Return to Baseline(28 days)
- Oxygenation - Ventilator Free Days(28 days)
- Change From Baseline in WHO Ordinal Severity Scale as a Categorical Improvement or Worsening(7 days)
- Oxygenation - Pulse Oximetry(Baseline through Day 10)