Study of RV521 for the treatment of adults who have received a blood cell transplant and that have a respiratory infection caused by the virus RSV

Randomized, double-blind, placebo-controlled trial of the safety, tolerability, and efficacy of RV521 in the treatment of adult subjects who have undergone hematopoietic cell transplantation (HCT) with a documented upper respiratory tract infection (URTI) with respiratory syncytial virus (RSV)

Status

Not yet recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2019-003746-33-FR

Enrollment

200

Registered

2020-05-20

Start date

2020-09-30

Completion date

Unknown

Last updated

2020-10-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Symptomatic RSV infection (upper airway involvement only) in subjects who have undergone HCT transplantation within 1 year of Randomization and who are moderately to severely immunocompromised. MedDRA version: 21.1 Level: PT Classification code 10035732 Term: Pneumonia respiratory syncytial viral System Organ Class: 10021881 - Infections and infestations MedDRA version: 20.0 Level: HLGT Classification code 10024970 Term: Respiratory tract infections System Organ Class: 10038738 - Respiratory,

Interventions

Product Code: RV521 Pharmaceutical Form: Capsule INN or Proposed INN: Sisunatovir Current Sponsor code: RV521 Hydrochloride, RV521.HCl Other descriptive name: RV521 Concentration unit: mg milligram(s)

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1 Has undergone autologous or allogeneic HCT using any conditioning regimen within 1 year of randomization. Subjects who have undergone HCT more than 1 year before Randomization are eligible if all other inclusion/exclusion criteria are satisfied and under at least one of the following conditions: a Diagnosed with Chronic Graft-vs-Host Disease (GVHD), or b Has used systemic corticosteroids in the 30 days prior to RSV infection 2 Has moderate to severe immunocompromise, defined as a score = 5 on the ISI-RSV and/or an ALC of = 500 cells/ mm3 3 Documentation of positive RSV infection in the upper airway Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 180 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20

Exclusion criteria

Exclusion criteria: 1 Use of non-marketed investigational agents within 30 days, OR use of an investigational monoclonal anti-RSV antibodies within 4 months or 5 half-lives of screening, whichever is longer, OR use of any investigational RSV vaccines after HCT. 2 Receiving a prescription, OTC, or herbal medication that is a potent inducer or inhibitor of CYP3A4, within 2 weeks of Randomization. 3 Receiving a prescription, OTC, or herbal medication that is a substrate of CYP3A4 with a narrow therapeutic index where monitoring blood levels is not possible. 4 Known chronic infection with hepatitis B, C, or HIV. 5 Is in the pre-engraftment period during RSV infection. 6 Admitted to the hospital primarily for lower respiratory tract disease of any cause as determined by the Investigator. 7 Any condition requiring mechanical ventilation or vasopressor support at the time of randomization. 8 Clinically significant bacteremia or fungemia within 5 days prior to Screening that has not been adequately treated. 9 Clinically significant bacterial, fungal, or viral pneumonia within 2 weeks prior to Screening that has not been adequately treated. 10 Excessive nausea/vomiting at Screening or an inability to swallow capsules. 11 Elevation of hepatic enzymes or renal compromise.

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate clinical improvement relative to placebo, defined as the proportion of subjects who do not experience lower respiratory tract complications (LRTC) during the study period And To compare the anti-viral activity of RV521 to that of placebo, measured by time weighted average change in viral load (DAVG) measured by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) from nasal swab samples. ;Secondary Objective: To evaluate clinical improvement relative to placebo as defined by duration of RSV-related symptoms over 28 days To evaluate the anti-viral effect of RV521 defined as the timeweighted average change in viral load (DAVG) measured by a cell-based infectivity assay (CBIA) from nasal swab samples To evaluate the proportion of days with lowest daily pulse oximetry oxygen saturation (SpO2) = 90% on room air To evaluate the requirements for respiratory supportive measures (oxygen and/or mechanical ventilation) and hospitalization/intensive care unit (ICU) utilization To compare the rates of mortality between subjects receiving RV521 to those receiving placebo To evaluate the safety and tolerability of RV521 in subjects with RSV URTI To evaluate of the pharmacokinetics/pharmacodynamic (PK/PD) relationship of RV521 treatment in adults with RSV URTI. ;Primary end point(s): 1 Proportion of subjects with a progression to Lower Respiratory Tract Complication (LRTC) during the study [ Time Frame: Pre-dose baseline (Day 1) through Visit 8 (Day 28) ] Progression to LRTC during the study defined as one of the following: Primary LRTI caused by RSV Secondary bacterial LRTI LRTI caused by another pathogen LRTC of unknown etiology 2 Change in RSV nasal viral load (via RT-qPCR) [ Time Frame: Pre-dose baseline (Day 1) through study completion; up to Visit 8 (Day 28) ] RSV change measured by the time-weighted average (DAVG) viral load using RT qPCR ;Timepoint(s) of evaluation of this end point: 1 Pre-dose baseline (Day 1) throug	—

Measure

Time frame

Main Objective: To evaluate clinical improvement relative to placebo, defined as the proportion of subjects who do not experience lower respiratory tract complications (LRTC) during the study period And To compare the anti-viral activity of RV521 to that of placebo, measured by time weighted average change in viral load (DAVG) measured by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) from nasal swab samples. ;Secondary Objective: To evaluate clinical improvement relative to placebo as defined by duration of RSV-related symptoms over 28 days To evaluate the anti-viral effect of RV521 defined as the timeweighted average change in viral load (DAVG) measured by a cell-based infectivity assay (CBIA) from nasal swab samples To evaluate the proportion of days with lowest daily pulse oximetry oxygen saturation (SpO2) = 90% on room air To evaluate the requirements for respiratory supportive measures (oxygen and/or mechanical ventilation) and hospitalization/intensive care unit (ICU) utilization To compare the rates of mortality between subjects receiving RV521 to those receiving placebo To evaluate the safety and tolerability of RV521 in subjects with RSV URTI To evaluate of the pharmacokinetics/pharmacodynamic (PK/PD) relationship of RV521 treatment in adults with RSV URTI. ;Primary end point(s): 1 Proportion of subjects with a progression to Lower Respiratory Tract Complication (LRTC) during the study [ Time Frame: Pre-dose baseline (Day 1) through Visit 8 (Day 28) ] Progression to LRTC during the study defined as one of the following: Primary LRTI caused by RSV Secondary bacterial LRTI LRTI caused by another pathogen LRTC of unknown etiology 2 Change in RSV nasal viral load (via RT-qPCR) [ Time Frame: Pre-dose baseline (Day 1) through study completion; up to Visit 8 (Day 28) ] RSV change measured by the time-weighted average (DAVG) viral load using RT qPCR ;Timepoint(s) of evaluation of this end point: 1 Pre-dose baseline (Day 1) throug

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Secondary

Measure	Time frame
Secondary end point(s): 1 Percent of participants who experience AEs, TEAEs, SAEs and withdrawals due to TEAEs. 2 Evaluate safety and tolerability of RV521 by assessing changes from baseline in systolic and diastolic BP (vital sign parameters). 3 Evaluate safety and tolerability of RV521 by assessing changes from baseline in body temperature (vital sign parameters). 4 Evaluate safety and tolerability of RV521 by assessing changes from baseline in respiration rate (vital sign parameters). 5 Evaluate safety and tolerability of RV521 by assessing changes from baseline in pulse/heart rate (vital sign parameters). 6 Evaluate safety and tolerability of RV521 by assessing changes from baseline weight/BMI Weight and height will be collected and combined to report BMI 7 Evaluate the proportion of subjects with changes and shifts in hematology/clinical chemistry/urinalysis laboratory values (laboratory tests read by a central lab) from baseline. 8 Evaluate the proportion of subjects with changes in ECG measurements and changes in clinical impression from baseline 9 Relationship between plasma exposures of RV521 and RSV viral loads measured in nasal swabs by RT-qPCR. 10 Relationship between plasma exposures of RV521 and RSV viral loads measured in nasal swabs by CBIA. 11 Mean change in RSV viral load assessed via CBIA 12 Mean change from baseline in viral RNA shedding 13 Proportion of subjects who no longer shed RSV assessed by both RT-qPCR and CBIA 14 Time to improvement in RSV-related symptoms 15 Time to total resolution of all RSV-related symptoms 16 Proportion of days with lowest daily SpO2 = 90% on room air SpO2 measured at every visit. For subjects on oxygen or who are mechanically ventilated may have this waived. 17 Number of days where supplementary oxygen was required Use of daily supplementary oxygen will be collected throughout the study. 18 Proportion of subjects who require hospitalization during the study 19 Mean number of days of	—

Measure

Time frame

Secondary end point(s): 1 Percent of participants who experience AEs, TEAEs, SAEs and withdrawals due to TEAEs. 2 Evaluate safety and tolerability of RV521 by assessing changes from baseline in systolic and diastolic BP (vital sign parameters). 3 Evaluate safety and tolerability of RV521 by assessing changes from baseline in body temperature (vital sign parameters). 4 Evaluate safety and tolerability of RV521 by assessing changes from baseline in respiration rate (vital sign parameters). 5 Evaluate safety and tolerability of RV521 by assessing changes from baseline in pulse/heart rate (vital sign parameters). 6 Evaluate safety and tolerability of RV521 by assessing changes from baseline weight/BMI Weight and height will be collected and combined to report BMI 7 Evaluate the proportion of subjects with changes and shifts in hematology/clinical chemistry/urinalysis laboratory values (laboratory tests read by a central lab) from baseline. 8 Evaluate the proportion of subjects with changes in ECG measurements and changes in clinical impression from baseline 9 Relationship between plasma exposures of RV521 and RSV viral loads measured in nasal swabs by RT-qPCR. 10 Relationship between plasma exposures of RV521 and RSV viral loads measured in nasal swabs by CBIA. 11 Mean change in RSV viral load assessed via CBIA 12 Mean change from baseline in viral RNA shedding 13 Proportion of subjects who no longer shed RSV assessed by both RT-qPCR and CBIA 14 Time to improvement in RSV-related symptoms 15 Time to total resolution of all RSV-related symptoms 16 Proportion of days with lowest daily SpO2 = 90% on room air SpO2 measured at every visit. For subjects on oxygen or who are mechanically ventilated may have this waived. 17 Number of days where supplementary oxygen was required Use of daily supplementary oxygen will be collected throughout the study. 18 Proportion of subjects who require hospitalization during the study 19 Mean number of days of

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Countries

Argentina, Australia, Belgium, Brazil, Canada, Chile, France, Israel, Italy, Korea, Democratic People's Republic of, Malaysia, Spain, Taiwan, United States

Contacts

Public ContactClinical Trial Information

ReViral Ltd.

hwelch@reviral.co.uk

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026