RSV Infection
Conditions
Brief summary
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.
Interventions
DRUGObeldesivir
Tablet administered orally
Tablet administered orally
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Exhibits at least 1 of the following risk factors for severe RSV disease: 1. Age ≥ 60 years 2. Moderate or severe chronic obstructive pulmonary disease (COPD) with a history of exacerbation during the preceding 12 months. 3. Asthma with a history of ≥ 1 exacerbation during the proceeding 12 months 4. One or more of the following chronic lung diseases: * i) Bronchiectasis * ii) Interstitial lung disease (eg, idiopathic pulmonary fibrosis) * iii) Pulmonary hypertension 5. 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. Key
Exclusion criteria
* 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Alleviation of Targeted Respiratory Syncytial Virus (RSV) Symptoms as Measured by Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Through Day 15 | 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) | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to RSV-Related Hospitalization or All-Cause Death Through Day 29 | Up to Day 29 | RSV-related hospitalization is defined as ≥ 24 hours of acute care for a reason related to RSV, in a hospital or similar acute care facility, including emergency rooms or temporary facilities instituted to address medical needs of those with RSV. RSV relatedness was determined by investigator. KM estimates were used in analysis. |
| Time to RSV-Related Medically Attended Visit or All-Cause Death Through Day 29 | Up to Day 29 | Medically attended visits (MAV) are defined as any interactions with health care professionals other than study staff or designees, including hospitalization; in-person emergency, urgent, or primary care visits; or any other in-person visit attended by the participant and a health care professional. RSV relatedness was determined by the investigator. KM estimates were used in analysis. |
| RSV Viral Load At Baseline | Baseline | The RSV viral load results were obtained from UTM (universal transport medium) nasal swab samples collected at Baseline. |
| Change From Baseline in RSV Viral Load Through Day 3 | Baseline, Day 3 | The RSV viral load results were obtained from UTM nasal swab samples collected at Baseline and Day 3. |
| Change From Baseline in RSV Viral Load Through Day 5 | Baseline, Day 5 | The RSV viral load results were obtained from UTM nasal swab samples collected at Baseline and Day 5. |
| Change From Baseline in RSV Viral Load Through Day 7 | Baseline, Day 7 | The RSV viral load results were obtained from UTM nasal swab samples collected at Baseline and Day 7. |
| Change From Baseline in RSV Viral Load Through Day 10 | Baseline, Day 10 | The RSV viral load results were obtained from UTM nasal swab samples collected at Baseline and Day 10. |
| Pharmacokinetic (PK) Parameter: AUCtau of GS-441524, Metabolite of Obeldesivir | Day 5: Pre-dose and at multiple timepoints (up to 12 hours) post-dose | AUCtau is defined as area under the plasma concentration-time curve during a dosing interval. |
| Change From Baseline in RSV Viral Load Through Day 15 | Baseline, Day 15 | The RSV viral load results were obtained from UTM nasal swab samples collected at Baseline and Day 15. |
| PK Parameter: Ctrough of GS-441524, Metabolite of Obeldesivir | Day 5 (predose) | Ctrough is defined as the concentration at the end of the dosing interval. |
| 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) | Cmax is defined as the maximum observed concentration of drug in plasma. |
| Time to Sustained Alleviation of Targeted RSV Symptoms as Measured by RiiQ Through Day 15 | Up to Day 15 | RiiQ and targeted RSV symptoms are defined in Outcome Measure #1. Each symptom is rated on scale of None, Mild, Moderate, \& Severe. Sustained alleviation of targeted RSV symptoms was defined similarly to alleviation of targeted RSV symptoms but for 3 consecutive assessments. Time to sustained alleviation of targeted RSV symptoms by Day 15 for participants with sustained 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 sustained symptom alleviation (censored), time was calculated as last date/time on which RiiQ was assessed minus first dose date/time. |
| Time to RSV-Related Lower Respiratory Tract Infection (LRTI) Through Day 29 | Up to Day 29 | RiiQ is defined in Outcome Measure #1. Lower Respiratory Tract (LRT) symptoms included cough, expectoration, shortness of breath, and wheezing. Based on RiiQ, RSV-related LRTI was defined as \>=2 of the following symptoms, 1 of which must be reported as at least 'moderate' severity: new or increased cough, new or increased wheezing, new or increased shortness of breath, new or increased expectoration and participant has not met alleviation endpoints. The time to RSV-related LRTI by Day 29 for participants with RSV-related LRTI, was calculated as date/time of meeting LRTI definition minus first dose date/time. For participants who completed Day 29 of the study or discontinued from the study before Day 29 without RSV-related LRTI (censored), time was calculated as last date/time on which RiiQ was assessed minus the first dose date/time. |
Countries
United States
Contacts
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States.
Pre-assignment details
168 participants were screened.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 47 Participants |
| Age, Categorical Between 18 and 65 years | 100 Participants |
| Age, Continuous | 54 years STANDARD_DEVIATION 16.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 57 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 129 Participants |
| Region of Enrollment United States | 74 Participants |
| Respiratory Syncytial Virus (RSV) Viral Load in Universal Transport Medium (UTM) | 4.84 log10 copies/mL STANDARD_DEVIATION 2.029 |
| Sex: Female, Male Female | 82 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 75 | 0 / 75 |
| other Total, other adverse events | 0 / 74 | 0 / 74 |
| serious Total, serious adverse events | 0 / 74 | 1 / 74 |
Outcome results
None listed