A Phase 1b/2a Study in Participants With Early Stage COVID-19 to Evaluate the Safety, Efficacy, and Pharmacokinetics of Remdesivir Administered by Inhalation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 156
- 试验地点
- 27
- 主要终点
- Time-weighted Average Change From Baseline in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 7
研究概览
简要总结
The primary objective of this study is to characterize the impact of inhaled remdesivir (RDV) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in participants with early stage coronavirus disease 2019 (COVID-19).
详细描述
This study will have multiple parts: Part A, Part B, and Part C. Part B will be conducted if supported by evaluation in healthy volunteers in another Phase 1a Gilead study (GS-US-553-9018). Participants in Part C will be enrolled after review of preliminary safety and available efficacy data from Parts A and B through at least Day 7.
GS-US-553-9018 is a Phase 1a randomized, blinded, placebo-controlled, single- and multiple-dose study in healthy volunteers to evaluate the safety, tolerability, and pharmacokinetics of remdesivir administered by inhalation.
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
- •Willing and able to provide written informed consent, or with a legal representative who can provide informed consent
- •SARS-CoV-2 infection first confirmed by polymerase chain reaction (PCR) (Parts A and B) or by nucleic acid testing or direct antigen testing (Part C) with sample collected ≤ 4 days prior to randomization
- •COVID-19 symptom onset ≤ 7 days prior to randomization
- •Oxygen saturation as measured by pulse oximetry (SpO2) > 94% on room air
排除标准
- •Ongoing or prior participation in any other clinical trial of an experimental vaccine or treatment for COVID-19
- •Prior or current hospitalization for COVID-19 or need for hospitalization
- •Treatment of COVID-19 with other agents with actual or possible direct antiviral activity against SARS-CoV-2 including intravenous (IV) RDV or administration of any SARS-CoV-2 (or COVID-19) vaccine
- •Participants chronically administered chloroquine or hydroxychloroquine for any reason are to be excluded
- •Requiring oxygen supplementation
- •Positive pregnancy test
- •Breastfeeding female
- •Known hypersensitivity to the study treatment, its metabolites, or formulation excipient
- •Pre-existing pulmonary conditions such as chronic obstructive pulmonary disease or asthma (Parts A and B only)
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
RDV + Placebo, Part A
Participants will receive inhaled RDV 31 mg administered daily for 3 days followed by placebo to match RDV daily for 2 days.
干预措施: Placebo (Drug)
Placebo, Part A
Participants will receive placebo to match inhaled RDV in Part A daily for 5 days.
干预措施: Placebo (Drug)
Remdesivir (RDV), Part A
Participants will receive inhaled RDV 31 mg administered daily for 5 days.
干预措施: Remdesivir (RDV) (Drug)
RDV + Placebo, Part A
Participants will receive inhaled RDV 31 mg administered daily for 3 days followed by placebo to match RDV daily for 2 days.
干预措施: Remdesivir (RDV) (Drug)
RDV, Part B
Participants will receive inhaled RDV 62 mg administered daily for up to 5 days.
干预措施: Remdesivir (RDV) (Drug)
RDV + Placebo, Part B
Participants will receive inhaled RDV 62 mg administered daily for up to 3 days followed by placebo to match RDV daily for 2 days.
干预措施: Remdesivir (RDV) (Drug)
RDV + Placebo, Part B
Participants will receive inhaled RDV 62 mg administered daily for up to 3 days followed by placebo to match RDV daily for 2 days.
干预措施: Placebo (Drug)
Placebo, Part B
Participants will receive placebo to match inhaled RDV in Part B daily for 5 days.
干预措施: Placebo (Drug)
RDV, Part C
Participants will receive inhaled RDV 39 mg administered daily for 5 days.
干预措施: Remdesivir (RDV) (Drug)
Placebo, Part C
Participants will receive placebo to match inhaled RDV in Part C daily for 5 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Time-weighted Average Change From Baseline in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 7
时间窗: Baseline, Day 7
Time-weighted average change in SARS-CoV-2 viral load was defined as area under the concentration versus time curve (AUC) of viral load change divided by time between baseline through Day 7.
Time-weighted Average Change From Baseline in Saliva SARS-CoV-2 Viral Load Through Day 7
时间窗: Baseline, Day 7
Time-weighted average change in SARS-CoV-2 viral load was defined as AUC of viral load change divided by time between baseline through Day 7.
Time-weighted Average Change From Baseline in Oropharyngeal SARS-CoV-2 Viral Load Through Day 7
时间窗: Baseline, Day 7
Time-weighted average change in SARS-CoV-2 viral load was defined as AUC of viral load change divided by time between baseline through Day 7.
次要结局
- Percentage of Participants With Treatment-Emergent Laboratory Abnormalities as Per Severity Grade(First dose date up to 5 days plus 30 days)
- Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)(First dose date up to 5 days plus 30 days)
- Percentage of Participants With Treatment-Emergent Adverse Events Leading to Study Treatment Discontinuation(First dose date up to 5 days plus 30 days)
- Number of Participants With All-Cause Medically Attended Visits (MAVs) or Death by Day 28(Randomization up to Day 28)
- Number of Participants With COVID-19 Related MAVs or Death by Day 28(Randomization up to Day 28)
- Number of Participants With Hospitalization by Day 28(Day 1 up to Day 28)
- Pharmacokinetic (PK) Parameter: AUC0-24h of Remdesivir (RDV) and Its Metabolites (GS-441524 and GS-704277) in Parts A and B(Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.)
- PK Parameter: AUClast of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B(Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.)
- PK Parameter: CLss/F of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B(Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.)
- PK Parameter: t1/2 of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B(Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.)
- PK Parameter: Vz/F of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B(Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.)
- PK Parameter: Cmax of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B(Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.)
- PK Parameter: Tmax of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B(Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.)
- PK Parameter: Clast of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B(Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.)
- PK Parameter: Tlast of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B(Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.)
- PK Parameter: AUCtau of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B(Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.)
- Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5(Baseline, Day 5)
- PK Parameter: λz of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B(Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.)
- Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 5(Baseline, Day 5)
- PK Parameter: Ctau of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B(Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.)
- Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5(Baseline, Day 5)
- Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7(Baseline, Day 7)
- Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7(Baseline, Day 7)
- Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 7(Baseline, Day 7)
- Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B(Baseline, Day 14)
- Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B(Baseline, Day 14)
- Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B(Baseline, Day 14)
- Time to Negative Nasopharyngeal SARS-CoV-2 Polymerase Chain Reaction (PCR)(Baseline up to Day 17)
- Time to Negative Oropharyngeal SARS-CoV-2 Polymerase Chain Reaction (PCR)(Baseline up to Day 17)
- Time to Negative Saliva SARS-CoV-2 Polymerase Chain Reaction (PCR)(Baseline up to Day 17)
- Time to Alleviation (Mild or Absent) of Baseline COVID-19 Symptoms as Reported on the COVID-19 Adapted InFLUenza Patient-Reported Outcome (FLU-PRO©) Questionnaire in Part C(First dose date up to Day 14)