Trial Outcomes & Findings for Efficacy, Pharmacokinetics, and Safety of Presatovir in Hospitalized Adults With Respiratory Syncytial Virus (RSV) Infection (NCT NCT02135614)

Last Updated: 2018-09-24

Results Overview

The time-weighted average change, often referred to as the DAVG, provides the average viral burden change from baseline. The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factor.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

189 participants

Primary outcome timeframe

Baseline to Day 5

Results posted on

2018-09-24

Participant Flow

Participants were enrolled at study sites in Australia, Europe, Asia, New Zealand, and the United States. The first participant was screened on 09 June 2014. The last study visit occurred on 12 April 2017.

833 participants were screened.

Participant milestones

Participant milestones
Measure	Presatovir Single dose of presatovir 200 mg (4 x 50 mg tablets)	Placebo Single dose of placebo tablets
Overall Study STARTED	94	95
Overall Study COMPLETED	86	90
Overall Study NOT COMPLETED	8	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Presatovir Single dose of presatovir 200 mg (4 x 50 mg tablets)	Placebo Single dose of placebo tablets
Overall Study Randomized but Not Treated	2	1
Overall Study Adverse Event	0	1
Overall Study Death	1	0
Overall Study Investigator's Discretion	0	1
Overall Study Withdrew Consent	2	2
Overall Study Lost to Follow-up	3	0

Baseline Characteristics

Efficacy, Pharmacokinetics, and Safety of Presatovir in Hospitalized Adults With Respiratory Syncytial Virus (RSV) Infection

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Presatovir n=92 Participants Single dose of presatovir 200 mg (4 x 50 mg tablets)	Placebo n=94 Participants Single dose of placebo tablets	Total n=186 Participants Total of all reporting groups
Age, Continuous	69.4 years STANDARD_DEVIATION 14.24 • n=5 Participants	65.9 years STANDARD_DEVIATION 13.87 • n=7 Participants	67.6 years STANDARD_DEVIATION 14.13 • n=5 Participants
Sex: Female, Male Female	50 Participants n=5 Participants	52 Participants n=7 Participants	102 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	42 Participants n=7 Participants	84 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	6 Participants n=5 Participants	11 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	72 Participants n=5 Participants	69 Participants n=7 Participants	141 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Not Permitted	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	85 Participants n=5 Participants	91 Participants n=7 Participants	176 Participants n=5 Participants
Region of Enrollment New Zealand	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Region of Enrollment Netherlands	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment South Korea	5 Participants n=5 Participants	11 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment Belgium	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Region of Enrollment Poland	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Italy	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United Kingdom	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Israel	32 Participants n=5 Participants	26 Participants n=7 Participants	58 Participants n=5 Participants
Region of Enrollment Australia	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment France	18 Participants n=5 Participants	17 Participants n=7 Participants	35 Participants n=5 Participants
Stratification Factor: Disease Status Asthma	22 Participants n=5 Participants	22 Participants n=7 Participants	44 Participants n=5 Participants
Stratification Factor: Disease Status Chronic Obstructive Pulmonary Disease	27 Participants n=5 Participants	30 Participants n=7 Participants	57 Participants n=5 Participants
Stratification Factor: Disease Status No Chronic Airways or Lung Disease	31 Participants n=5 Participants	31 Participants n=7 Participants	62 Participants n=5 Participants
Stratification Factor: Disease Status Other Chronic Airways or Lung Disease	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Nasal Viral Load	5.58 log10 copies/mL STANDARD_DEVIATION 2.104 • n=5 Participants	5.07 log10 copies/mL STANDARD_DEVIATION 2.528 • n=7 Participants	5.32 log10 copies/mL STANDARD_DEVIATION 2.337 • n=5 Participants
Flu-PRO score	1.11 units on a scale STANDARD_DEVIATION 0.553 • n=5 Participants	1.04 units on a scale STANDARD_DEVIATION 0.566 • n=7 Participants	1.07 units on a scale STANDARD_DEVIATION 0.559 • n=5 Participants
Duration of Hospitalization Prior to First Dose	2.9 days STANDARD_DEVIATION 3.14 • n=5 Participants	3.2 days STANDARD_DEVIATION 7.13 • n=7 Participants	3.0 days STANDARD_DEVIATION 5.52 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Day 5

Population: Evaluable Analysis Set: all randomized participants who received at least 1 dose of study medication, had an RSV viral load greater than lower limit of quantification (LLOQ) of the RT-qPCR assay in the Day 1 nasal-swab sample, and had a minimum of 3 quantifiable samples (including baseline) within a 5 day period.

Outcome measures

Outcome measures
Measure	Presatovir n=80 Participants Single dose of presatovir 200 mg (4 x 50 mg tablets)	Placebo n=74 Participants Single dose of placebo tablets
Time-Weighted Average Change in Respiratory Syncytial Viral (RSV) Load From Baseline to Day 5	-0.77 log10 copies/mL Standard Error 0.113	-0.89 log10 copies/mL Standard Error 0.118

SECONDARY outcome

Timeframe: Baseline to Day 5

Population: Participants in the Evaluable Analysis Set with available data were analyzed.

The Flu-PRO is a patient-reported outcome questionnaire utilized as a standardized method for evaluating symptoms of influenza. Flu-PRO Score was calculated as the mean of 38 individual scores. Individual scores ranged from 0 (no symptoms) to 4 (worst symptoms). The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factor.

Outcome measures

Outcome measures
Measure	Presatovir n=79 Participants Single dose of presatovir 200 mg (4 x 50 mg tablets)	Placebo n=74 Participants Single dose of placebo tablets
Time-weighted Average Change in the Flu-PRO Score From Baseline to Day 5	-0.27 units on a scale Standard Error 0.029	-0.35 units on a scale Standard Error 0.030

SECONDARY outcome

Timeframe: Up to Day 28

Outcome measures

Outcome measures
Measure	Presatovir n=80 Participants Single dose of presatovir 200 mg (4 x 50 mg tablets)	Placebo n=74 Participants Single dose of placebo tablets
Number of Hospitalization-Free Days Following Presatovir Administration	25 days Interval 20.0 to 27.0	25 days Interval 20.0 to 27.0

SECONDARY outcome

Timeframe: Up to Day 28

The adjusted rate of unplanned medical encounters (clinic visits, emergency room visits, urgent care visits, and rehospitalizations) related to a respiratory illness after initial hospital discharge through Day 28 will be assessed. Event rate was calculated as the total number of unplanned medical encounters divided by the total number of participants. The mean values presented were adjusted for stratification factor.

Outcome measures

Outcome measures
Measure	Presatovir n=80 Participants Single dose of presatovir 200 mg (4 x 50 mg tablets)	Placebo n=74 Participants Single dose of placebo tablets
Rate of Unplanned Medical Encounters	0.226 encounters per participant Interval 0.133 to 0.384	0.066 encounters per participant Interval 0.029 to 0.15

Adverse Events

Presatovir

Serious events: 8 serious events

Other events: 34 other events

Deaths: 2 deaths

Placebo

Serious events: 13 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Presatovir n=92 participants at risk Single dose of presatovir 200 mg (4 x 50 mg tablets)	Placebo n=94 participants at risk Single dose of placebo tablets
Gastrointestinal disorders Abdominal pain	5.4% 5/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	2.1% 2/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Gastrointestinal disorders Constipation	4.3% 4/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	5.3% 5/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	5.4% 5/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	7.4% 7/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Gastrointestinal disorders Nausea	4.3% 4/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	9.6% 9/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Gastrointestinal disorders Vomiting	2.2% 2/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	6.4% 6/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
General disorders Asthenia	5.4% 5/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	1.1% 1/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Investigations Alanine aminotransferase increased	5.4% 5/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	2.1% 2/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Nervous system disorders Headache	8.7% 8/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	5.3% 5/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.5% 6/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	3.2% 3/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.2% 2/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	5.3% 5/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER

Measure	Presatovir n=92 participants at risk Single dose of presatovir 200 mg (4 x 50 mg tablets)	Placebo n=94 participants at risk Single dose of placebo tablets
Cardiac disorders Angina pectoris	1.1% 1/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	0.00% 0/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Cardiac disorders Cardiac failure congestive	2.2% 2/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	0.00% 0/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Cardiac disorders Myocardial infarction	0.00% 0/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	1.1% 1/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Eye disorders Angle closure glaucoma	0.00% 0/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	1.1% 1/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
General disorders Asthenia	0.00% 0/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	1.1% 1/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
General disorders Non-cardiac chest pain	1.1% 1/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	0.00% 0/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Infections and infestations Cellulitis	0.00% 0/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	1.1% 1/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Infections and infestations Gastroenteritis	0.00% 0/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	1.1% 1/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Infections and infestations Infective exacerbation of chronic obstructive airways disease	1.1% 1/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	0.00% 0/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Infections and infestations Influenza	0.00% 0/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	1.1% 1/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Infections and infestations Pneumonia	1.1% 1/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	0.00% 0/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Investigations Troponin increased	1.1% 1/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	0.00% 0/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	1.1% 1/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Product Issues Device malfunction	0.00% 0/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	1.1% 1/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Reproductive system and breast disorders Prostatitis	0.00% 0/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	1.1% 1/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	1.1% 1/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	1.1% 1/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	0.00% 0/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.1% 1/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	2.1% 2/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.1% 1/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	0.00% 0/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	0.00% 0/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	1.1% 1/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/92 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.	1.1% 1/94 • Up to Day 28 Safety Analysis Set: all participants who received 1 dose of study drug.