A Phase 2 Randomized, Placebo-controlled Study of the Safety and Efficacy of Obeldesivir to Treat Nonhospitalized Adults With Acute Respiratory Syncytial Virus (RSV) Infection
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 150
- 试验地点
- 231
- 主要终点
- Time to Alleviation of Targeted Respiratory Syncytial Virus (RSV) Symptoms as Measured by Respiratory Infection Intensity and Impact Questionnaire (RiiQ) through Day 15
研究概览
简要总结
The goal of this clinical study was to learn more about the study drug, obeldesivir (ODV; GS-5245), and how safe and effective it was in treating nonhospitalized adults with acute respiratory syncytial virus (RSV) infection. The researchers wanted to see if obeldesivir can help participants' symptoms get better faster.
The primary objectives of this study were to evaluate the efficacy of ODV in reducing the duration of symptoms and to evaluate the safety and tolerability of ODV in nonhospitalized adult participants with acute RSV infection.
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
- •Exhibits at least 1 of the following risk factors for severe RSV disease:
- •Age ≥ 60 years
- •Moderate or severe chronic obstructive pulmonary disease (COPD) with a history of exacerbation during the preceding 12 months.
- •Asthma with a history of ≥ 1 exacerbation during the proceeding 12 months
- •One or more of the following chronic lung diseases:
- •i) Bronchiectasis
- •ii) Interstitial lung disease (eg, idiopathic pulmonary fibrosis)
- •iii) Pulmonary hypertension
- •Chronic cardiovascular disease exclusive of hypertension
- •RSV infection confirmed ≤ 3 days before randomization
- •New onset or increased from baseline of ≥ 2 of the following signs and or/symptoms, and at least 1 sign/symptom of moderate severity at screening, and onset ≤ 3 days before randomization.
- •a) Nasal congestion.
- •b) Sore throat.
- •c) Cough.
- •d) Wheezing.
- •e) Shortness of breath (ie, dyspnea).
- •f) Expectoration (ie, sputum production).
- •RSV vaccine status:
- •Individuals whose only risk factor is age ≥ 60 years must not have received any doses of a vaccine for RSV.
排除标准
- •Currently requiring or expected to require hospitalization within 48 hours after randomization.
- •Documented previous infection and/or hospitalization for RSV during the current respiratory virus season.
- •Documented to be positive for influenza A or B virus, and/or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ≤ 7 days prior to randomization.
- •Concurrent infections requiring treatment with any systemic antimicrobial therapy ≤ 7 days prior to randomization.
- •Individuals with a history of cystic fibrosis.
- •Undergoing dialysis, known history of moderate or severe renal impairment within the preceding 6 months prior to randomization.
- •Pregnant at screening.
- •Received any approved or authorized, direct-acting antiviral drug or monoclonal antibody against RSV < 28 days or < 5 half-lives, whichever is longer, before randomization.
- •Received an investigational product < 28 days or < 5 half-lives, whichever is longer, before randomization.
- •Alanine aminotransferase ≥ 5 x upper limit of normal within 6 months prior to randomization, unless confirmed as resolved at screening.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Obeldesivir (ODV)
Participants will receive obeldesivir for 5 days
干预措施: Obeldesivir (Drug)
结局指标
主要结局
Time to Alleviation of Targeted Respiratory Syncytial Virus (RSV) Symptoms as Measured by Respiratory Infection Intensity and Impact Questionnaire (RiiQ) through Day 15
时间窗: Day 1 up to Day 15
The RiiQ symptom scale is a 13-item questionnaire rated on a 4-point scale. Each symptom is rated on a scale of 0 to 3 where 0=None, 1=Mild, 2=Moderate, and 3=Severe. Higher scores indicated greater severity.
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) Through Day 29
时间窗: Up to 29 days
Percentage of Participants Experiencing Laboratory Abnormalities Through Day 29
时间窗: Up to 29 days
Percentage of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Study Drug Discontinuation
时间窗: First dose date up to Day 60
Time to Alleviation of Targeted Respiratory Syncytial Virus (RSV) Symptoms as Measured by Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Through Day 15
时间窗: Up to Day 15
RiiQ symptom scale is 13-item questionnaire (6 symptoms related to upper \& lower respiratory tract \& 7 systemic symptoms).Targeted RSV symptoms are 6 respiratory symptoms: nasal congestion, sore throat, cough, expectoration, shortness of breath \& wheezing.Each symptom is rated on scale of None, Mild, Moderate \& Severe.Alleviation of targeted RSV symptoms was defined as for 2 consecutive assessments: non-preexisting symptoms scored was None or Mild; pre-existing symptoms that were present but not worse at baseline scored same or below;\& pre-existing symptoms that were worse at baseline improved at least one scale grade level. Time to alleviation of targeted RSV symptoms by Day 15 for participants with symptom alleviation was calculated as symptom alleviation date/time minus first dose date/time.For participants who completed or discontinued study by Day 15 without symptom alleviation (censored),time was calculated as last date/time on which RiiQ was assessed minus first dose date/time.
Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to 5 days plus 30 days
An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a study drug that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not the AE is considered related to the study drug. TEAEs were defined as any AE that began on or after the date of first dose of study drug up to the date of last dose of study drug plus 30 days and that led to study drug discontinuation. Percentages are rounded off.
Percentage of Participants Who Experienced Treatment-emergent Laboratory Abnormalities
时间窗: Up to 5 days plus 30 days
Treatment-emergent laboratory abnormalities are defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point up to the date of the last dose of study drug plus 30 days. The Division of AIDS (DAIDS) Toxicity Grading Scale, Version 2.1 was used to assign toxicity grades (0 to 4) to laboratory results for analysis. Grade 0 included all values that did not meet the criteria for an abnormality of at least Grade 1. Grade 1: mild, Grade 2: moderate, Grade 3: severe, and Grade 4: potentially life-threatening. Percentage are rounded off.
Percentage of Participants Who Experienced Serious Adverse Events
时间窗: Up to 5 days plus 30 days
A serious adverse event (SAEs) is defined as an event that, at any dose, results in death, a life-threatening situation, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or a medically important event or reaction. Percentage was rounded off.
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation
时间窗: Up to 5 days plus 30 days
TEAEs were defined as any AE that began on or after the date of first dose of study drug up to the date of last dose of study drug plus 30 days and that led to study drug discontinuation. Percentages are rounded off.
次要结局
- Time to Sustained Alleviation of Targeted RSV Symptoms as Measured by RiiQ Through Day 15(Day 1 up to Day 15)
- Time to RSV-Related Lower Respiratory Tract Infection (LRTI) Through Day 29(Day 1 up to Day 29)
- Time to RSV-Related Hospitalization or all-Cause Death Through Day 29(Day 1 up to Day 29)
- Change from Baseline in RSV Viral Load Through Day 15(Baseline, Day 15)
- Time to RSV-Related Medically Attended Visit (MAVs) or all-Cause Death Through Day 29(Day 1 up to Day 29)
- Change from baseline in RSV Viral Load Through Day 3(Baseline, Day 3)
- Change from Baseline in RSV Viral Load Through Day 5(Baseline, Day 5)
- Change from Baseline in RSV Viral Load Through Day 7(Baseline, Day 7)
- Change from Baseline in RSV Viral Load Through Day 10(Baseline, Day 10)
- Pharmacokinetic (PK) Parameter: AUCtau of GS-441524(Day 1 to Day 5)
- PK Parameter: Ctrough of GS-441524(Day 1 to Day 5)
- PK Parameter: Cmax of GS-441524(Day 1 to Day 5)
- Change From Baseline in RSV Viral Load Through Day 15(Baseline, Day 15)
- Time to Sustained Alleviation of Targeted RSV Symptoms as Measured by RiiQ Through Day 15(Up to Day 15)
- Time to RSV-Related Lower Respiratory Tract Infection (LRTI) Through Day 29(Up to Day 29)
- Time to RSV-Related Hospitalization or All-Cause Death Through Day 29(Up to Day 29)
- Change From Baseline in RSV Viral Load Through Day 10(Baseline, Day 10)
- Time to RSV-Related Medically Attended Visit or All-Cause Death Through Day 29(Up to Day 29)
- RSV Viral Load At Baseline(Baseline)
- Change From Baseline in RSV Viral Load Through Day 3(Baseline, Day 3)
- Change From Baseline in RSV Viral Load Through Day 5(Baseline, Day 5)
- Change From Baseline in RSV Viral Load Through Day 7(Baseline, Day 7)
- Pharmacokinetic (PK) Parameter: AUCtau of GS-441524, Metabolite of Obeldesivir(Day 5: Pre-dose and at multiple timepoints (up to 12 hours) post-dose)
- PK Parameter: Ctrough of GS-441524, Metabolite of Obeldesivir(Day 5 (predose))
- PK Parameter: Cmax of GS-441524, Metabolite of Obeldesivir(Day 1 (At multiple timepoints [up to 4 hours] post-dose); Day 5 (Pre-dose and at multiple timepoints [up to 4 hours] post-dose))