A Phase 1b Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Safety, Pharmacokinetics, and Anti-viral Effects of Galidesivir Administered Via Intravenous Infusion to Subjects With Yellow Fever or COVID-19
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 24
- 试验地点
- 5
- 主要终点
- exposure of galidesivir as measured by plasma concentrations
研究概览
简要总结
This is a placebo-controlled, randomized, double-blind study to evaluate the pharmacokinetics, safety and antiviral activity of galidesivir in subjects with yellow fever (YF) or COVID-19.
详细描述
This is a randomized, double-blind, placebo-controlled study to evaluate the pharmacokinetics (PK), safety, and antiviral effects of galidesivir administered via intravenous (IV) infusion vs. placebo in hospitalized adult subjects with either Yellow Fever (Group A) or COVID-19 (Group B). The study will be conducted in two parts, and each Group (A or B) will proceed independently through the study. Part 1 is a dose ranging study with three sequential cohorts of eight patients each that will be randomized 3:1 to receive IV galidesivir or placebo every 12 hours for 7 days. Upon completion of part 1, an optimized dosing regimen of galidesivir will be selected for part 2, based on part 1 results including safety, PK, viral load reduction, and improvement in signs and symptoms and clinical manifestations, and mortality. In part 2, up to 42 patients will be randomized 2:1 to receive IV galidesivir or placebo. After treatment, the patients will remain hospitalized until resolution of symptoms allows release. All patients will be followed for mortality through Day 56.
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
- Double (Participant, Investigator)
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
- •Group A - Yellow Fever
- •Ability to provide written informed consent
- •Males and nonpregnant, non-breast-feeding females, aged 18 years or older
- •Subject weight ≥ 50 kg (110 lb.)
- •Positive test for YFV by molecular amplification of the virus in the blood
- •First onset of symptoms of YF occurring within the previous 7 days
- •Male and female subjects must agree to the contraception requirements and must meet the inclusion criteria regarding contraception as outlined in the protocol
- •CLCR of at least 60 mL/min by Cockcroft-Gault equation
- •AST < 5000 u/L
- •Indirect bilirubin < 1.5 mg/dL
- •Neutrophil count < 7500 /mm3
- •International Normalized Ratio (INR) < 1.5
排除标准
- •Group A - Yellow Fever
- •Any clinically significant medical condition or medical history that, in the opinion of the investigator or sponsor, would interfere with the subject's ability to participate in the study or increase the risk of participation for that subject
- •Employment by the study site, or an immediate family relationship to either study site employees or Sponsor employee
- •Lack of suitable veins for venipuncture/cannulation as assessed by the Investigator at Screening
- •Participation in any other investigational drug or vaccine study currently or within the past 30 days
- •Diagnosis of YF vaccine-related viscerotropic disease
- •Subjects with hepatic encephalopathy as defined by Conn Score ≥
- •Subject has severe immunosuppression or immunodeficiency, leukemia, lymphoma, thymic disease, generalized malignancy, or radiation therapy (within the past 3 months), or is undergoing current treatment with immunosuppressive drugs, defined as drugs that impair immune responses to infections
- •A treatment plan for YF that would include concomitant administration of antiviral medications
- •Inclusion Criteria Group B - COVID-19
- •Ability to provide written informed consent, accept randomization to any assigned treatment arm, and comply with planned study procedures
- •Males and nonpregnant, non-breast-feeding females, aged 18 years or older
- •Male and female subjects must agree to the contraception requirements and must meet the inclusion criteria regarding contraception as outlined in the protocol
- •Subject weight ≥ 50 kg (110 lb.)
- •Clinical syndrome consistent with moderate-severe (but not critically ill) COVID-19, defined by at least one of the following:
- •Symptoms of acute viral lower respiratory tract infection, such as fever, non-productive cough, dyspnea, and either 1) a pulse oximetry oxygen saturation (SpO2) ≤ 94% or a respiratory rate > 24 breaths/minute as measured at rest without use of supplemental oxygen or 2) a clinical requirement for supplemental oxygen treatment or non-invasive mechanical ventilation
- •Radiographic pulmonary findings seen on chest imaging (chest X-ray or computed tomography [CT scan]) consistent with COVID-19
- •Positive test for SARS-CoV-2 by molecular amplification of the virus in a respiratory specimen (nasopharyngeal, oropharyngeal, lower respiratory tract [eg, expectorated sputum]) collected < 96 hours prior to randomization. Note: subjects may have a positive test recorded prior to screening if they are admitted to the hospital with a presumed case of COVID-19
- •Exclusion Criteria: Group B - COVID-19
- •Any clinically significant medical condition or medical history that, in the opinion of the investigator or sponsor, would interfere with the subject's ability to participate in the study or increase the risk of participation for the subject
- •Lack of suitable veins for venipuncture/cannulation as assessed by the Investigator at Screening
- •Participation in any other investigational drug or vaccine study currently or within the past 30 days
- •A clinical treatment plan that would include concomitant administration of any other experimental treatment or off-label use of marketed medications that are intended as specific treatment for the COVID-19 clinical syndrome or the SARS-CoV-2 infection. Any such medications must be discontinued prior to study enrollment, unless a formal written standard of care policy document from the national, state, or institutional authorities requires otherwise.
- •Severe or rapidly progressive disease or medical condition of any type such that death is an expected or likely outcome within 72 hours or that would require referral or transfer to another medical facility
- •Severe renal impairment (estimated glomerular filtration rate (eGFR) ≤ 50 mL/min/1.73m2) or receiving continuous renal replacement therapy, hemodialysis, or peritoneal dialysis
- •Severe liver disease by medical history or ALT or AST > 5 times upper limit of normal
- •Congestive heart failure by medical history ≥ Class 3
- •Requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) at the time of randomization
研究组 & 干预措施
Galidesivir
Galidesivir IV infusion
干预措施: Galidesivir (Drug)
Placebo
Placebo IV infusion
干预措施: Placebo (Drug)
结局指标
主要结局
exposure of galidesivir as measured by plasma concentrations
时间窗: 24 hours post dose on Day 1 through 12 hours post dose on Day 7
number of subjects with change in laboratory parameters
时间窗: absolute number and change from baseline through the end of the study, approximately 56 days
number of subjects with treatment emergent adverse events and serious adverse events
时间窗: absolute number through the end of the study, approximately 56 days
次要结局
- yellow fever virus (YFV) titer (Group A)(change in YFV titer from baseline through Day 21)
- antiviral effect on SARS-CoV-2 in the respiratory tract - COVID-19 (Group B)(change in SARS-CoV-2 from baseline through Day 21)
- changes from baseline and time to improvement using NEWS in COVID-19 (Group B)(through Day21)
- changes in clinical status using 8-point ordinal scale in COVID-19 (Group B)(through Day 21)
- mortality(mortality at Day 56)