Trial Outcomes & Findings for Presatovir in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus (RSV) Infection of the Lower Respiratory Tract (NCT NCT02254421)

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 factors.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

60 participants

Primary outcome timeframe

Baseline to Day 9

Results posted on

2018-09-24

Participant Flow

Participants were enrolled at study sites in Asia Pacific, Europe, and the United States. The first participant was screened on 31 January 2015. The last study visit occurred on 17 April 2017.

71 participants were screened.

Participant milestones

Participant milestones
Measure	Presatovir Presatovir 200 mg (4 x 50 mg tablets) on Days 1, 5, 9, 13, and 17 administered orally or via nasogastric tube	Placebo Placebo tablets on Days 1, 5, 9, 13, and 17 administered orally or via nasogastric tube
Overall Study STARTED	31	29
Overall Study COMPLETED	29	26
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Presatovir Presatovir 200 mg (4 x 50 mg tablets) on Days 1, 5, 9, 13, and 17 administered orally or via nasogastric tube	Placebo Placebo tablets on Days 1, 5, 9, 13, and 17 administered orally or via nasogastric tube
Overall Study Randomized but Not Treated	1	0
Overall Study Death	0	2
Overall Study Withdrew Consent	1	1

Baseline Characteristics

Presatovir in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus (RSV) Infection of the Lower Respiratory Tract

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Presatovir n=30 Participants Presatovir 200 mg (4 x 50 mg tablets) on Days 1, 5, 9, 13, and 17 administered orally or via nasogastric tube	Placebo n=29 Participants Placebo tablets on Days 1, 5, 9, 13, and 17 administered orally or via nasogastric tube	Total n=59 Participants Total of all reporting groups
Age, Continuous	50.5 years STANDARD_DEVIATION 16.27 • n=5 Participants	54.4 years STANDARD_DEVIATION 12.59 • n=7 Participants	52.4 years STANDARD_DEVIATION 14.58 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	23 Participants n=7 Participants	44 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized White	23 Participants n=5 Participants	18 Participants n=7 Participants	41 Participants n=5 Participants
Race/Ethnicity, Customized Not Permitted	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	23 Participants n=5 Participants	18 Participants n=7 Participants	41 Participants n=5 Participants
Region of Enrollment South Korea	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Sweden	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	27 Participants n=5 Participants	20 Participants n=7 Participants	47 Participants n=5 Participants
Region of Enrollment France	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Switzerland	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Stratification Factor: Supplemental O2 Requirement at Time of Randomization Supplemental O2 Requirement ≤ 2 L/min	19 Participants n=5 Participants	19 Participants n=7 Participants	38 Participants n=5 Participants
Stratification Factor: Supplemental O2 Requirement at Time of Randomization Supplemental O2 Requirement > 2 L/min	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Stratification Factor: Treatment of Current RSV Infection with Ribavirin Yes	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Stratification Factor: Treatment of Current RSV Infection with Ribavirin No	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Nasal Viral Load	6.22 log10 copies/mL STANDARD_DEVIATION 1.365 • n=5 Participants	6.02 log10 copies/mL STANDARD_DEVIATION 1.574 • n=7 Participants	6.12 log10 copies/mL STANDARD_DEVIATION 1.462 • n=5 Participants
Oxygen Saturation	94 percent saturation STANDARD_DEVIATION 3.8 • n=5 Participants	93 percent saturation STANDARD_DEVIATION 5.1 • n=7 Participants	93 percent saturation STANDARD_DEVIATION 4.5 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Day 9

Population: Full Analysis Set: all randomized participants who received at least 1 full dose of study drug and had an RSV viral load greater than or equal to the lower limit of quantification of the RT-qPCR assay in the Day 1 nasal sample, as determined by RT-qPCR at the central lab.

Outcome measures

Outcome measures
Measure	Presatovir n=29 Participants Presatovir 200 mg (4 x 50 mg tablets) on Days 1, 5, 9, 13, and 17 administered orally or via nasogastric tube	Placebo n=28 Participants Placebo tablets on Days 1, 5, 9, 13, and 17 administered orally or via nasogastric tube
Time-weighted Average Change in Nasal Respiratory Syncytial Viral (RSV) Load From Baseline to Day 9	-1.00 log10 copies/mL Standard Error 0.215	-0.97 log10 copies/mL Standard Error 0.218

SECONDARY outcome

Timeframe: Up to Day 28

Outcome measures

Outcome measures
Measure	Presatovir n=29 Participants Presatovir 200 mg (4 x 50 mg tablets) on Days 1, 5, 9, 13, and 17 administered orally or via nasogastric tube	Placebo n=28 Participants Placebo tablets on Days 1, 5, 9, 13, and 17 administered orally or via nasogastric tube
Number of Supplemental O2-Free Days Through Day 28	26 days Interval 10.0 to 28.0	28 days Interval 9.0 to 28.0

SECONDARY outcome

Timeframe: Up to Day 28

Outcome measures

Outcome measures
Measure	Presatovir n=29 Participants Presatovir 200 mg (4 x 50 mg tablets) on Days 1, 5, 9, 13, and 17 administered orally or via nasogastric tube	Placebo n=28 Participants Placebo tablets on Days 1, 5, 9, 13, and 17 administered orally or via nasogastric tube
Percentage of Participants Developing Respiratory Failure Requiring Mechanical Ventilation Through Day 28	10.3 percentage of participants Interval 2.2 to 27.4	10.7 percentage of participants Interval 2.3 to 28.2

SECONDARY outcome

Timeframe: Up to Day 28

Outcome measures

Outcome measures
Measure	Presatovir n=29 Participants Presatovir 200 mg (4 x 50 mg tablets) on Days 1, 5, 9, 13, and 17 administered orally or via nasogastric tube	Placebo n=28 Participants Placebo tablets on Days 1, 5, 9, 13, and 17 administered orally or via nasogastric tube
Percentage of All-Cause Mortality Among Participants Through Day 28	0.0 percentage of participants Interval 0.0 to 11.9	7.1 percentage of participants Interval 0.9 to 23.5

Adverse Events

Presatovir

Serious events: 7 serious events

Other events: 19 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 17 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

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=30 participants at risk Presatovir 200 mg (4 x 50 mg tablets) on Days 1, 5, 9, 13, and 17 administered orally or via nasogastric tube	Placebo n=29 participants at risk Placebo tablets on Days 1, 5, 9, 13, and 17 administered orally or via nasogastric tube
Blood and lymphatic system disorders Anaemia	0.00% 0/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	3.4% 1/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	3.4% 1/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Immune system disorders Graft versus host disease	3.3% 1/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	0.00% 0/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Infections and infestations Bacterial infection	0.00% 0/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	3.4% 1/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Infections and infestations Clostridium difficile colitis	0.00% 0/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	3.4% 1/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Infections and infestations Febrile infection	0.00% 0/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	3.4% 1/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Infections and infestations Influenza	3.3% 1/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	0.00% 0/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Infections and infestations Pneumonia	10.0% 3/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	6.9% 2/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Infections and infestations Sepsis	0.00% 0/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	3.4% 1/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute leukaemia	0.00% 0/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	3.4% 1/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Nervous system disorders Altered state of consciousness	0.00% 0/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	3.4% 1/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Nervous system disorders Cerebral infarction	3.3% 1/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	0.00% 0/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Nervous system disorders Cerebrovascular accident	3.3% 1/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	0.00% 0/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	3.3% 1/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	0.00% 0/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.3% 1/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	6.9% 2/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Vascular disorders Hypotension	0.00% 0/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	3.4% 1/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.

Measure	Presatovir n=30 participants at risk Presatovir 200 mg (4 x 50 mg tablets) on Days 1, 5, 9, 13, and 17 administered orally or via nasogastric tube	Placebo n=29 participants at risk Placebo tablets on Days 1, 5, 9, 13, and 17 administered orally or via nasogastric tube
Blood and lymphatic system disorders Anaemia	3.3% 1/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	10.3% 3/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Blood and lymphatic system disorders Lymphopenia	3.3% 1/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	6.9% 2/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Blood and lymphatic system disorders Neutropenia	0.00% 0/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	6.9% 2/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	3.3% 1/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	10.3% 3/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Cardiac disorders Atrial fibrillation	0.00% 0/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	6.9% 2/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Eye disorders Visual impairment	0.00% 0/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	6.9% 2/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Gastrointestinal disorders Diarrhoea	10.0% 3/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	10.3% 3/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Gastrointestinal disorders Dry mouth	6.7% 2/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	3.4% 1/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Gastrointestinal disorders Nausea	10.0% 3/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	3.4% 1/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
General disorders Fatigue	0.00% 0/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	6.9% 2/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
General disorders Non-cardiac chest pain	6.7% 2/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	0.00% 0/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
General disorders Oedema peripheral	3.3% 1/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	6.9% 2/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
General disorders Pyrexia	6.7% 2/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	10.3% 3/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Infections and infestations Acute sinusitis	10.0% 3/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	0.00% 0/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Investigations Alanine aminotransferase increased	10.0% 3/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	3.4% 1/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Investigations Aspartate aminotransferase increased	6.7% 2/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	3.4% 1/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Investigations Blood alkaline phosphatase increased	6.7% 2/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	0.00% 0/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Investigations Troponin T increased	0.00% 0/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	6.9% 2/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	10.0% 3/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	3.4% 1/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	6.9% 2/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Nervous system disorders Dizziness	0.00% 0/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	6.9% 2/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Nervous system disorders Headache	6.7% 2/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	10.3% 3/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Psychiatric disorders Anxiety	3.3% 1/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	6.9% 2/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Renal and urinary disorders Acute kidney injury	0.00% 0/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	6.9% 2/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	10.3% 3/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	10.0% 3/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	0.00% 0/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	6.7% 2/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	0.00% 0/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Skin and subcutaneous tissue disorders Rash	3.3% 1/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	6.9% 2/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.
Vascular disorders Hypotension	6.7% 2/30 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.	3.4% 1/29 • Up to Day 28 Safety Analysis Set: participants who received at least 1 full dose of study drug.