Back to resultsStudy of RV521 in the Treatment of Adult Subjects Who Have Undergone HCT With an URTI With RSV (REVIRAL2)
Primary Purpose
RSV Infection, Stem Cell Transplant Complications, Lower Resp Tract Infection
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
RV521 oral tablet
Placebo oral tablet
Sponsored by
About this trial
This is an interventional treatment trial for RSV Infection focused on measuring RV521, lower respiratory tract complication, HCT, hematopoietic cell transplantation, LRTI, Respiratory tract infection, immunocompromise
Eligibility Criteria
Inclusion Criteria:
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:
- Diagnosed with Chronic Graft-vs-Host Disease (GVHD), or
- Has used systemic corticosteroids in the 30 days prior to RSV infection
- Has moderate to severe immunocompromise, defined as a score ≥ 5 on the ISI-RSV and/or an ALC of ≤ 500 cells/ mm3
- Documentation of positive RSV infection in the upper airway
Exclusion Criteria:
- 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.
- Receiving a prescription, OTC, or herbal medication that is a potent inducer or inhibitor of CYP3A4, within 2 weeks of Randomization.
- 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.
- Known chronic infection with hepatitis B, C, or HIV.
- Is in the pre-engraftment period during RSV infection.
- Admitted to the hospital primarily for lower respiratory tract disease of any cause as determined by the Investigator.
- Any condition requiring mechanical ventilation or vasopressor support at the time of randomization.
- Clinically significant bacteremia or fungemia within 5 days prior to Screening that has not been adequately treated.
- Clinically significant bacterial, fungal, or viral pneumonia within 2 weeks prior to Screening that has not been adequately treated.
- Excessive nausea/vomiting at Screening or an inability to swallow capsules.
- Elevation of hepatic enzymes or renal compromise.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
RV521 Capsules
RV521 Placebo Capsules
Arm Description
RV521 is formulated as a dry powder blend of RV521 drug substance with mannitol as excipient. They are a white, opaque capsule and administered orally.
RV521 placebo capsules will contain mannitol and microcrystalline cellulose only. They are a white, opaque capsule and administered orally.
Outcomes
Primary Outcome Measures
Proportion of subjects with a progression to Lower Respiratory Tract Complication (LRTC) during the study
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
Change in RSV nasal viral load (via RT-qPCR)
RSV change measured by the time-weighted average (DAVG) viral load using RT qPCR
Secondary Outcome Measures
Percent of participants who experience AEs, TEAEs, SAEs and withdrawals due to TEAEs
Safety analyses will include a summary of AEs, including but not limited to n (%) of subjects in each treatment group and overall.
Evaluate safety and tolerability of RV521 by assessing changes from baseline in systolic and diastolic BP (vital sign parameters)
BP will be collected in mm Hg. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Evaluate safety and tolerability of RV521 by assessing changes from baseline in body temperature (vital sign parameters)
Body Temperature will be collected in degrees Fahrenheit (°F) or degrees Celsius (°C). Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Evaluate safety and tolerability of RV521 by assessing changes from baseline in respiration rate (vital sign parameters)
Respiration rate will be measured in breaths per minute. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Evaluate safety and tolerability of RV521 by assessing changes from baseline in pulse/heart rate (vital sign parameters)
Heart rate will be measured in beats per minute. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Evaluate safety and tolerability of RV521 by assessing changes from baseline weight/BMI
Weight and height will be collected and combined to report BMI
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.
Results at each visit will be summarized using the statistics n, mean, standard deviation, median, minimum and maximum. Also, change from baseline will also be summarized by post baseline visits.
Evaluate the proportion of subjects with changes in ECG measurements and changes in clinical impression from baseline
ECGs will be taken with a centrally supplied ECG machine and electronically transmitted to a central ECG repository. ECG will only be evaluated by the Investigator for normal, abnormal NCS and abnormal CS.
Parameters collected will be:
Ventricular Heart Rate (bpm)
PR Interval (msec)
QRS Interval (msec)
QT Interval (msec)
QTcB Interval (msec)
Results at each visit will be summarized using the statistics: n (number of observations), mean, SD, median, minimum and maximum.
Relationship between plasma exposures of RV521 and RSV viral loads measured in nasal swabs by RT-qPCR
Nasal swabs will be collected for analysis of viral load and RSV F protein gene sequencing at a central laboratory. Viral load will be assessed at intervals from nasal swabs by RT-qPCR.
Relationship between plasma exposures of RV521 and RSV viral loads measured in nasal swabs by CBIA
Nasal swabs will be collected for analysis of viral load and RSV F protein gene sequencing at a central laboratory. Viral load will be assessed at intervals from nasal swabs by CBIA.
Mean change in RSV viral load assessed via CBIA
change measured by the time weighted average (DAVG) viral load using CBIA
Mean change from baseline in viral RNA shedding
RSV assessed via nasal swabs collected at each visit and analyzed at a central laboratory.
Proportion of subjects who no longer shed RSV assessed by both RT-qPCR and CBIA at each timepoint
RSV assessed via nasal swabs collected at each visit and analyzed at a central laboratory.
Time to improvement in RSV-related symptoms
Defined as all symptoms present at initiation of therapy are mild or no longer present. (absent/resolved)
Time to total resolution of all RSV-related symptoms
Defined as all symptoms are no longer present.
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.
Number of days where supplementary oxygen was required
Use of daily supplementary oxygen will be collected throughout the study.
Proportion of subjects who require hospitalization during the study
Daily hospitalization utilization will be collected
Mean number of days of hospitalization during the study
Daily hospitalization utilization will be collected
Proportion of subjects requiring ICU
Daily ICU utilization will be collected
Mean number of days in ICU
Daily ICU utilization will be collected
Proportion of subjects requiring mechanical ventilation
Daily mechanical ventilation requirements will be collected
Number of subjects who experience death (all-cause mortality)
Patient outcome will be followed and collected
Number of subjects who experience death attributable to LRTC
Patient outcome will be followed and collected
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04267822
Brief Title
Study of RV521 in the Treatment of Adult Subjects Who Have Undergone HCT With an URTI With RSV
Acronym
REVIRAL2
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Withdrawn
Why Stopped
No recruitment
Study Start Date
June 15, 2020 (Anticipated)
Primary Completion Date
June 30, 2023 (Anticipated)
Study Completion Date
July 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
RV521 is to being developed to treat RSV infection and disease in susceptible individuals at high risk for complications. This is an international, multicenter, placebo-controlled study. Eligible subjects are adults with a documented symptomatic RSV infection who have undergone HCT transplantation and are moderately to severely immunocompromised. Qualified subjects will be randomized in a 1:1 ratio to receive RV521 or placebo, twice daily for 10 days.
Detailed Description
The purpose of this study is to compare the viral load, safety, tolerability, and clinical efficacy of RV521 compared to placebo. This is a Phase 2, international, multicenter, randomized, double-blind, placebo-controlled study. Up to 200 adult subjects with a documented symptomatic RSV URTI who have undergone HCT within 1 year of randomization and who are moderately to severely immunocompromised will be randomized.
Qualified subjects will be randomized in a 1:1 ratio to receive RV521 capsules or matching placebo twice daily for 10 days. After the completion of the 10-day double-blind treatment period, subjects will be followed for an additional 28 days. Study drug may be taken on an outpatient or inpatient basis, depending on clinical status and site practices. Randomization will be stratified by type of HCT graft and ALC count. There are 9 clinic visits planned for this study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
RSV Infection, Stem Cell Transplant Complications, Lower Resp Tract Infection
Keywords
RV521, lower respiratory tract complication, HCT, hematopoietic cell transplantation, LRTI, Respiratory tract infection, immunocompromise
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
A Phase 2, international, multicenter, randomized, double-blind, placebo-controlled study.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The Investigators, Sponsor, Independent Adjudication Committee members, and any personnel involved in the subject's care, assessment, monitoring, data collection, or analysis will be blinded to the subject treatment assignment throughout the conduct of the study. Exceptions to this are limited to a fire-walled-protected, unblinded Data Safety Monitoring Board (DSMB) statistician at the Contract Research Organization (CRO) who will prepare output for the closed session of all DSMB meetings.
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RV521 Capsules
Arm Type
Experimental
Arm Description
RV521 is formulated as a dry powder blend of RV521 drug substance with mannitol as excipient. They are a white, opaque capsule and administered orally.
Arm Title
RV521 Placebo Capsules
Arm Type
Placebo Comparator
Arm Description
RV521 placebo capsules will contain mannitol and microcrystalline cellulose only. They are a white, opaque capsule and administered orally.
Intervention Type
Drug
Intervention Name(s)
RV521 oral tablet
Other Intervention Name(s)
sisunatovir
Intervention Description
Each RV521 dose is four 50 mg dry powder blend capsules, taken orally twice daily for 10 days (20 doses total; 80 capsules total)
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Other Intervention Name(s)
vehicle
Intervention Description
Each placebo dose is four capsules, taken orally twice daily for 10 days (20 doses total; 80 capsules total)
Primary Outcome Measure Information:
Title
Proportion of subjects with a progression to Lower Respiratory Tract Complication (LRTC) during the study
Description
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
Time Frame
Pre-dose baseline (Day 1) through Visit 8 (Day 28)
Title
Change in RSV nasal viral load (via RT-qPCR)
Description
RSV change measured by the time-weighted average (DAVG) viral load using RT qPCR
Time Frame
Pre-dose baseline (Day 1) through study completion; up to Visit 8 (Day 28)
Secondary Outcome Measure Information:
Title
Percent of participants who experience AEs, TEAEs, SAEs and withdrawals due to TEAEs
Description
Safety analyses will include a summary of AEs, including but not limited to n (%) of subjects in each treatment group and overall.
Time Frame
First dose of study drug through Visit 8 (Day 28)
Title
Evaluate safety and tolerability of RV521 by assessing changes from baseline in systolic and diastolic BP (vital sign parameters)
Description
BP will be collected in mm Hg. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Time Frame
Baseline through Visit 8 (Day 28)
Title
Evaluate safety and tolerability of RV521 by assessing changes from baseline in body temperature (vital sign parameters)
Description
Body Temperature will be collected in degrees Fahrenheit (°F) or degrees Celsius (°C). Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Time Frame
Baseline through Visit 8 (Day 28)
Title
Evaluate safety and tolerability of RV521 by assessing changes from baseline in respiration rate (vital sign parameters)
Description
Respiration rate will be measured in breaths per minute. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Time Frame
Baseline through Visit 8 (Day 28)
Title
Evaluate safety and tolerability of RV521 by assessing changes from baseline in pulse/heart rate (vital sign parameters)
Description
Heart rate will be measured in beats per minute. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Time Frame
Baseline through Visit 8 (Day 28)
Title
Evaluate safety and tolerability of RV521 by assessing changes from baseline weight/BMI
Description
Weight and height will be collected and combined to report BMI
Time Frame
Baseline through Visit 8 (Day 28)
Title
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.
Description
Results at each visit will be summarized using the statistics n, mean, standard deviation, median, minimum and maximum. Also, change from baseline will also be summarized by post baseline visits.
Time Frame
Collected at Visit 2/Day 1 (pre-dose), Visit 4/Day 3, Visit 6/Day 14 and Visit 8/Day 28
Title
Evaluate the proportion of subjects with changes in ECG measurements and changes in clinical impression from baseline
Description
ECGs will be taken with a centrally supplied ECG machine and electronically transmitted to a central ECG repository. ECG will only be evaluated by the Investigator for normal, abnormal NCS and abnormal CS.
Parameters collected will be:
Ventricular Heart Rate (bpm)
PR Interval (msec)
QRS Interval (msec)
QT Interval (msec)
QTcB Interval (msec)
Results at each visit will be summarized using the statistics: n (number of observations), mean, SD, median, minimum and maximum.
Time Frame
Measurements will be taken at Day 1/Visit 2 (pre-dose and at 5-hours post-dose), on Day 3/Visit 4 (at 5 hours post-dose), and at Visit 6 (Day 14)
Title
Relationship between plasma exposures of RV521 and RSV viral loads measured in nasal swabs by RT-qPCR
Description
Nasal swabs will be collected for analysis of viral load and RSV F protein gene sequencing at a central laboratory. Viral load will be assessed at intervals from nasal swabs by RT-qPCR.
Time Frame
Pre-dose baseline (Day 1) and every visit through Visit 8 (Day 28)
Title
Relationship between plasma exposures of RV521 and RSV viral loads measured in nasal swabs by CBIA
Description
Nasal swabs will be collected for analysis of viral load and RSV F protein gene sequencing at a central laboratory. Viral load will be assessed at intervals from nasal swabs by CBIA.
Time Frame
Pre-dose baseline (Day 1) and every visit through Visit 8 (Day 28)
Title
Mean change in RSV viral load assessed via CBIA
Description
change measured by the time weighted average (DAVG) viral load using CBIA
Time Frame
Pre-dose baseline (Day 1) through study completion; up to Visit 8 (Day 28)
Title
Mean change from baseline in viral RNA shedding
Description
RSV assessed via nasal swabs collected at each visit and analyzed at a central laboratory.
Time Frame
Pre-dose baseline (Day 1) through study completion; up to Visit 8 (Day 28)
Title
Proportion of subjects who no longer shed RSV assessed by both RT-qPCR and CBIA at each timepoint
Description
RSV assessed via nasal swabs collected at each visit and analyzed at a central laboratory.
Time Frame
Pre-dose baseline (Day 1) through study completion; up to Visit 8 (Day 28)
Title
Time to improvement in RSV-related symptoms
Description
Defined as all symptoms present at initiation of therapy are mild or no longer present. (absent/resolved)
Time Frame
Daily from baseline (Day 1) through Visit 8 (Day 28)
Title
Time to total resolution of all RSV-related symptoms
Description
Defined as all symptoms are no longer present.
Time Frame
Daily from baseline (Day 1) through Visit 8 (Day 28)
Title
Proportion of days with lowest daily SpO2 ≥ 90% on room air
Description
SpO2 measured at every visit. For subjects on oxygen or who are mechanically ventilated may have this waived.
Time Frame
Daily from baseline (Day 1) through Visit 8 (Day 28)
Title
Number of days where supplementary oxygen was required
Description
Use of daily supplementary oxygen will be collected throughout the study.
Time Frame
Baseline (Day 1) through Visit 8 (Day 28)
Title
Proportion of subjects who require hospitalization during the study
Description
Daily hospitalization utilization will be collected
Time Frame
Baseline (Day 1) through Visit 8 (Day 28)
Title
Mean number of days of hospitalization during the study
Description
Daily hospitalization utilization will be collected
Time Frame
Baseline (Day 1) through Visit 8 (Day 28)
Title
Proportion of subjects requiring ICU
Description
Daily ICU utilization will be collected
Time Frame
Baseline (Day 1) through Visit 8 (Day 28)
Title
Mean number of days in ICU
Description
Daily ICU utilization will be collected
Time Frame
Baseline (Day 1) through Visit 8 (Day 28)
Title
Proportion of subjects requiring mechanical ventilation
Description
Daily mechanical ventilation requirements will be collected
Time Frame
Baseline (Day 1) through Visit 8 (Day 28)
Title
Number of subjects who experience death (all-cause mortality)
Description
Patient outcome will be followed and collected
Time Frame
First dose of study drug through Visit 8 (Day 28)
Title
Number of subjects who experience death attributable to LRTC
Description
Patient outcome will be followed and collected
Time Frame
First dose of study drug through Visit 8 (Day 28)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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:
Diagnosed with Chronic Graft-vs-Host Disease (GVHD), or
Has used systemic corticosteroids in the 30 days prior to RSV infection
Has moderate to severe immunocompromise, defined as a score ≥ 5 on the ISI-RSV and/or an ALC of ≤ 500 cells/ mm3
Documentation of positive RSV infection in the upper airway
Exclusion Criteria:
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.
Receiving a prescription, OTC, or herbal medication that is a potent inducer or inhibitor of CYP3A4, within 2 weeks of Randomization.
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.
Known chronic infection with hepatitis B, C, or HIV.
Is in the pre-engraftment period during RSV infection.
Admitted to the hospital primarily for lower respiratory tract disease of any cause as determined by the Investigator.
Any condition requiring mechanical ventilation or vasopressor support at the time of randomization.
Clinically significant bacteremia or fungemia within 5 days prior to Screening that has not been adequately treated.
Clinically significant bacterial, fungal, or viral pneumonia within 2 weeks prior to Screening that has not been adequately treated.
Excessive nausea/vomiting at Screening or an inability to swallow capsules.
Elevation of hepatic enzymes or renal compromise.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
PfizerCT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Learn more about this trial
Study of RV521 in the Treatment of Adult Subjects Who Have Undergone HCT With an URTI With RSV
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