A Phase II Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Antiviral Activity, Safety, Pharmacokinetics, and Efficacy of RO7496998 (AT-527) in Non-Hospitalized Adult Patients With Mild or Moderate COVID-19
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 104
- 试验地点
- 12
- 主要终点
- Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 550 mg and Matched Placebo
研究概览
简要总结
This randomized study evaluates the antiviral activity, safety, efficacy and pharmacokinetics of AT-527 versus a placebo in participants with mild or moderate coronavirus disease (COVID-19) who are not hospitalized.
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
- •Positive SARS-CoV-2 diagnostic test (RT-PCR or rapid antigen test)at screening
- •Has symptoms consistent with mild or moderate COVID-19, as determined by the investigator, with onset ≤5 days prior to randomization
排除标准
- •Clinical signs indicative of COVID-19 illness requiring hospitalization, defined as any of the following: shortness of breath at rest, respiratory rate ≥30, heart rate ≥125, peripheral capillary oxygen saturation ≤93% on room air
- •Treatment with a therapeutic agent against SARS-CoV-2 including, but not limited to, other direct acting antivirals, convalescent plasma, monoclonal antibodies against SARS CoV-2, or intravenous immunoglobulin within 3 months or less than 5 drug elimination half-lives (whichever is longer) prior to screening
- •Requirement, in the opinion of the investigator, for any of the prohibited medications during the study
- •Use of hydroxychloroquine or amiodarone within 3 months of screening
- •Pregnant or breastfeeding, or intending to become pregnant during the study or within 30 days after the final dose of AT-
- •Women of childbearing potential must have a negative urine pregnancy test result at screening
- •Abnormal laboratory test results at screening
- •Clinically significant abnormal ECG, as determined by the Investigator, at screening
- •Planned procedure or surgery during the study
- •Known allergy or hypersensitivity to study drug or drug product excipients
- •Substance abuse, as determined by the investigator, within 12 months prior to screening
- •Poor peripheral venous access
- •Malabsorption syndrome or other condition that would interfere with enteral absorption
- •Any clinically significant history of epistaxis within the last 3 months and/or history of being hospitalized due to epistaxis of any previous occasion
- •History of anaphylaxis
- •Any uncontrolled serious medical condition or other clinically significant abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
研究组 & 干预措施
AT-527 1100 mg (4x275 mg)
Participants will receive 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
干预措施: AT-527 (Drug)
Placebo
Participants will receive AT-527-matched placebo twice a day (BID) on Days 1-5.
干预措施: Placebo (Drug)
AT-527 550 mg (1x550 mg)
Participants will receive 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.
干预措施: AT-527 (Drug)
结局指标
主要结局
Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 550 mg and Matched Placebo
时间窗: Baseline, Day 3, Day 5, Day 7
SARS-CoV-2 virus RNA was measured by reverse-transcription polymerase chain reaction (RT-PCR) from nasopharyngeal (NP) swabs. The change from baseline was estimated from an ANCOVA model with baseline viral load as a covariate. Reported here is the adjusted mean change from baseline. A negative change from baseline indicates an improvement.
Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 1100 mg and Pooled Placebo
时间窗: Baseline, Day 3, Day 5, Day 7
SARS-CoV-2 virus RNA was measured by reverse-transcription polymerase chain reaction (RT-PCR) from NP swabs. The change from baseline was estimated from an ANCOVA model with baseline viral load as a covariate. Reported here is the adjusted mean change from baseline. A negative change from baseline indicates an improvement.
次要结局
- Time to Cessation of SARS-CoV-2 Viral Shedding(Up to Day 7)
- Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA(Baseline, Day 3, Day 5, Day 7)
- Time to Alleviation of COVID-19 Symptoms (43 Hours)(Up to 28 Days)
- Percentage of Participants With Adverse Events (AEs)(Up to 33 Days)
- Time to Sustained Non-Detectable SARS-CoV-2 Virus RNA(Up to Day 7)
- Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints(Baseline, Day 3, Day 5, Day 7)
- Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours)(Up to 28 Days)
- Duration of Fever(Up to 28 Days)
- Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527(Day 1: pre-dose, 1 hour, 4 hours; Day 3: pre-dose; Day 5: pre-dose, 1 hour, 4 hours, 48 hours)
- Time to Alleviation of COVID-19 Symptoms (21.5 Hours)(Up to 28 Days)
- Percentage of Participants With COVID-19 Related Complications(Up to 33 Days)
- Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527(Day 1: pre-dose, 1 hour, 3 hours; Day 3: pre-dose; Day 5: pre-dose, 3 hours, 48 hours)
- Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours)(Up to 28 Days)
- Time to Alleviation of an Individual Symptom(Up to 28 Days)