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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04225897




Registration number
NCT04225897
Ethics application status
Date submitted
11/12/2019
Date registered
13/01/2020
Date last updated
6/03/2020

Titles & IDs
Public title
A Study in Infants With RSV LRTI to Evaluate RV521
Scientific title
A Phase 2a Open-Label Study in Infants With REspiratory Syncytial VIRus Lower RespirAtory Tract Infection, Followed by a DoubLe-blind, Placebo-controlled Part, to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Effect of RV521 (REVIRAL 1)
Secondary ID [1] 0 0
REVC003
Universal Trial Number (UTN)
Trial acronym
REVIRAL 1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Respiratory Syncytial Virus (RSV) 0 0
Lower Resp Tract Infection 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - RV521
Treatment: Drugs - Placebo

Experimental: RV521 - sisunatovir is formulated as a dry powder blend of RV521 drug substance with mannitol as excipient. The RV521 dry powder blend will be supplied in capsules containing 10, 20, or 50 mg RV521. The Investigational Medicinal Product (IMP) will be dispersed in a defined volume of water prior to oral administration on a mg/kg basis. Instructions for opening the capsule(s) and dispersing the contents in a fixed volume of water prior to administration will be provided in the Pharmacy Manual.
The proposed dosing regimen for Part A is a single open label dose of RV521. Part B and C is RV521 or placebo administered BID, 12 hours apart, for a period of 5 consecutive days with a total of 10 doses. However, this is subject to the recommendation of the DSMC.

Placebo Comparator: Placebo - The placebo capsules administered in Part B and C will contain mannitol and microcrystalline cellulose (vehicle). The placebo dry powder will be dispersed in water and given orally BID. Instructions for opening the capsule(s) and dispersing the contents in a fixed volume of water prior to administration will be provided in the Pharmacy Manual.


Treatment: Drugs: RV521
RV521 is an RSV F protein inhibitor administered orally

Treatment: Drugs: Placebo
vehicle administered orally

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing incidence of AEs, TEAEs, SAEs, and withdrawals due to TEAEs. - Summary tables of AEs will be based on TEAEs, defined as events starting, or worsening, after the first dose of IMP.
Timepoint [1] 0 0
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary outcome [2] 0 0
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing changes in physical examinations. - Results at each visit will be summarised using the statistics: n (number of observations), mean, SD, median, minimum and maximum.
Timepoint [2] 0 0
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary outcome [3] 0 0
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing systolic BP (vital sign parameters) and changes from baseline - Baseline characteristics will be summarized descriptively by treatment. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Timepoint [3] 0 0
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary outcome [4] 0 0
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing diastolic BP (vital sign parameters) and changes from baseline - Baseline characteristics will be summarized descriptively by treatment. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Timepoint [4] 0 0
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary outcome [5] 0 0
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing body temperature (vital sign parameters) and changes from baseline - Baseline characteristics will be summarized descriptively by treatment. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Timepoint [5] 0 0
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary outcome [6] 0 0
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing respiration rate (vital sign parameters) and changes from baseline - Baseline characteristics will be summarized descriptively by treatment. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Timepoint [6] 0 0
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary outcome [7] 0 0
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing heart rate (vital sign parameters) and changes from baseline - Baseline characteristics will be summarized descriptively by treatment. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Timepoint [7] 0 0
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary outcome [8] 0 0
To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing pulse oximetry (vital sign parameters) and changes from baseline - Baseline characteristics will be summarized descriptively by treatment. Quantitative variables will be summarized used the statistics n, mean, standard deviation, median, minimum and maximum.
Timepoint [8] 0 0
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary outcome [9] 0 0
Number of participants with changes in haematology/clinical chemistry/urinalysis laboratory values (laboratory tests read by a central lab) from baseline in Part A and Part B. - Results at each visit will be summarised using the statistics n, mean, standard deviation, median, minimum and maximum. Also, change from baseline will also be summarised by post baseline visits.
Timepoint [9] 0 0
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary outcome [10] 0 0
Number of participants with changes in ECG measurements from baseline in Part A and Part B - 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 summarised using the statistics: n (number of observations), mean, SD, median, minimum and maximum.
Timepoint [10] 0 0
48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Primary outcome [11] 0 0
Part C: Evaluate the effect of RV521, compared to placebo, on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to show time to resolution of symptoms. - Overall time to resolution of RSV-related signs and symptoms will be calculated from the time of randomization to the time that they are no longer present (absent or severity =0), and will be summarized and analysed as Time to Improvement.
Timepoint [11] 0 0
up to 48 hours post dose 10
Primary outcome [12] 0 0
Part C: Evaluate the effect (efficacy) of RV521, compared to placebo, on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to assess time to change of symptoms. - Time to change in symptoms will be calculated for RSV-related signs and symptoms that are classified as moderate or severe during the course of the study and will be defined as the time from randomization until no longer present (absent or severity=0) or mild (scores = 5).
Timepoint [12] 0 0
up to 48 hours post dose 10
Primary outcome [13] 0 0
Part C: Evaluate the effect (efficacy) of RV521, compared to placebo, on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to assess change in severity of symptoms - Change in severity of symptoms by RV521, compared to placebo, will be measured by a composite score over time.
Timepoint [13] 0 0
up to 48 hours post dose 10
Primary outcome [14] 0 0
Part C: Evaluate the effect (efficacy) of RV521, compared to placebo, on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to assess use of supplemental oxygen. - Duration and maximum level of O2 provided will be assessed.
Timepoint [14] 0 0
up to 48 hours post dose 10
Secondary outcome [1] 0 0
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing time to maximum plasma concentration (tmax). - Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Timepoint [1] 0 0
48 hours post dose 1 (Part A)
Secondary outcome [2] 0 0
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing maximum observed plasma concentration (Cmax). - Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Timepoint [2] 0 0
48 hours post dose 1 (Part A)
Secondary outcome [3] 0 0
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing area under the plasma concentration time curve from time zero to 12 hours (AUC0-12). - Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Timepoint [3] 0 0
48 hours post dose 1 (Part A)
Secondary outcome [4] 0 0
To characterise the PK of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing the area under the plasma concentration time curve from time zero to last measurable plasma concentration (AUC0 t). - Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Timepoint [4] 0 0
48 hours post dose 1 (Part A)
Secondary outcome [5] 0 0
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing terminal half-life (t1/2). - Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Timepoint [5] 0 0
48 hours post dose 1 (Part A)
Secondary outcome [6] 0 0
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing area under the plasma concentration time curve from time zero to infinity (AUC0-8). - Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Timepoint [6] 0 0
48 hours post dose 1 (Part A)
Secondary outcome [7] 0 0
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing predicted plasma clearance. - Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Timepoint [7] 0 0
48 hours post dose 1 (Part A)
Secondary outcome [8] 0 0
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing apparent volume of distribution of the drug after extravascular administration (V/F). - Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Timepoint [8] 0 0
48 hours post dose 1 (Part A)
Secondary outcome [9] 0 0
To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing trough concentration at the end of first dosing interval (C12) (data permitting). - Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Timepoint [9] 0 0
48 hours post dose 1 (Part A)
Secondary outcome [10] 0 0
To characterise the pharmacokinetics (PK) of multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing accumulation ratio, percent fluctuation. - Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Timepoint [10] 0 0
48 hours post dose 10
Secondary outcome [11] 0 0
To characterise the pharmacokinetics (PK) of multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing the area under the plasma concentration time curve from time zero to the end of last dosing interval (AUC0-tau). - Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Timepoint [11] 0 0
48 hours post dose 10
Secondary outcome [12] 0 0
To characterise the pharmacokinetics (PK) of multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing average plasma concentration over dosing interval (Cave). - Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Timepoint [12] 0 0
48 hours post dose 10
Secondary outcome [13] 0 0
To characterise the pharmacokinetics (PK) of multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing minimum observed plasma concentration (Cmin). - Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Timepoint [13] 0 0
48 hours post dose 10
Secondary outcome [14] 0 0
To characterise the pharmacokinetics (PK) of multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI by assessing plasma trough concentration (Ctrough). - Pharmacokinetic analysis will include listings and summaries of PK concentrations by time point, derived PK, parameters and analysis of relationship with dose and body weight.
Timepoint [14] 0 0
48 hours post dose 10
Secondary outcome [15] 0 0
Part B: To evaluate the antiviral effects of RV521 in infants hospitalised with RSV LRTI by RSV viral load measured in nasopharyngeal swabs by RT qPCR. - Pharmacodynamics analysis will include listing of results of viral load with summary statistics by dose level and time point.
Timepoint [15] 0 0
up to 48 hours post dose 10
Secondary outcome [16] 0 0
Part B: To evaluate the antiviral effects of RV521 in infants hospitalised with RSV LRTI by RSV viral load measured in nasopharyngeal swabs by CBIA. - Pharmacodynamics analysis will include listing of results of viral load with summary statistics by dose level and time point.
Timepoint [16] 0 0
up to 48 hours post dose 10
Secondary outcome [17] 0 0
Part B: Evaluate the effect of RV521 compared to placebo on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to assess time to resolution of symptoms. - Overall Time to Resolution of RSV-related signs and symptoms will be calculated from the time of randomization to the time that they are no longer present (absent or severity =0), and will be summarized and analysed as for Time to Improvement.
Timepoint [17] 0 0
48 hours post dose 10
Secondary outcome [18] 0 0
Part B: Evaluate the effect of RV521 compared to placebo on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to assess time to improvement evaluated by change in severity of symptoms. - Time to improvement will be calculated for RSV-related signs and symptoms that are classified as moderate or severe during the course of the study and will be defined as the time from randomization until no longer present (absent or severity=0) or mild (scores = 5).
Timepoint [18] 0 0
48 hours post dose 10
Secondary outcome [19] 0 0
Part B: Evaluate the effect of RV521 compared to placebo on the clinical course of RSV LRTI using the RSV Clinical Scoring System and the Adapted Version of ReSVinet Scale to assess change in severity of symptoms. - Change in severity of symptoms by RV521, compared to placebo, will be measured by a composite score over time.
Timepoint [19] 0 0
48 hours post dose 10

Eligibility
Key inclusion criteria
1. Male or female = 1 month and = 36 months of age

2. Weight = 3.5 kg

3. Clinical diagnosis of LRTI

4. A positive RSV diagnostic test

5. Hospitalised because of RSV LRTI

6. Symptoms of LRTI must be present for no more than 1 week (Part B) and no more than 5
days (Part C) before the Screening Visit

7. Expected to remain in hospital for a minimum of 3 days

8. The parent(s)/legal guardian(s) of the subject have provided written informed consent
for the subject to participate and are able and willing to comply with the study
protocol
Minimum age
1 Month
Maximum age
36 Months
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Premature (gestational age less than 37 weeks) AND <1 year of post-natal age

2. Known to have significant comorbidities that would limit the ability to administer
study drug or evaluate the safety or clinical response to study drug.

3. Any clinically significant ECG abnormalities.

4. Known to be immunocompromised.

5. High risk of having developing asthma.

6. Suspected of having a clinically significant bacterial infection.

7. History of renal failure.

8. Clinical evidence of hepatic decompensation

9. History of epilepsy or seizures, including febrile seizures

10. Allergy to test medication or constituents

11. Has received 1 or more doses of palivizumab at any time before Screening or received
treatment with antiviral therapy for RSV (eg, ribavirin or intravenous [IV]
immunoglobulin) within 3 months before the Screening Visit.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Argentina
State/province [2] 0 0
Ciudad Autonoma de Buenos Aires
Country [3] 0 0
Argentina
State/province [3] 0 0
San Miguel De Tucumán
Country [4] 0 0
Chile
State/province [4] 0 0
Region De Los Lagos
Country [5] 0 0
Chile
State/province [5] 0 0
Los Ángeles
Country [6] 0 0
Chile
State/province [6] 0 0
Osorno
Country [7] 0 0
Chile
State/province [7] 0 0
Santiago
Country [8] 0 0
Costa Rica
State/province [8] 0 0
San Jose
Country [9] 0 0
Costa Rica
State/province [9] 0 0
San José
Country [10] 0 0
Hungary
State/province [10] 0 0
Csongrad
Country [11] 0 0
Hungary
State/province [11] 0 0
Budapest
Country [12] 0 0
Malaysia
State/province [12] 0 0
Kelantan
Country [13] 0 0
Malaysia
State/province [13] 0 0
Pulau Pinang
Country [14] 0 0
Malaysia
State/province [14] 0 0
Terengganu
Country [15] 0 0
New Zealand
State/province [15] 0 0
Wellington
Country [16] 0 0
Panama
State/province [16] 0 0
San Pablo Viejo
Country [17] 0 0
Panama
State/province [17] 0 0
Panama City
Country [18] 0 0
Philippines
State/province [18] 0 0
National Capital Region
Country [19] 0 0
Poland
State/province [19] 0 0
Woj. Lodzkie
Country [20] 0 0
Poland
State/province [20] 0 0
Woj. Mazowieckie
Country [21] 0 0
Poland
State/province [21] 0 0
Woj. Wielkopolskie
Country [22] 0 0
Poland
State/province [22] 0 0
Woj.Malopolskie
Country [23] 0 0
Taiwan
State/province [23] 0 0
Hualien City
Country [24] 0 0
Taiwan
State/province [24] 0 0
Kaohsiung City
Country [25] 0 0
Taiwan
State/province [25] 0 0
Tainan City
Country [26] 0 0
Thailand
State/province [26] 0 0
Bangkok
Country [27] 0 0
Thailand
State/province [27] 0 0
Chiang Mai
Country [28] 0 0
Thailand
State/province [28] 0 0
Phitsanulok

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ReViral Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a multicentre, 3-part study to evaluate safety, tolerability, PK, PD, and antiviral
effect of single and multiple dosing of RV521 in infants hospitalised due to Respiratory
Syncytial Virus (RSV) lower respiratory tract infection (LRTI). Due to the adaptive study
design, the number of enrolled subjects may vary depending on the obtained PK and safety
profiles.
Trial website
https://clinicaltrials.gov/show/NCT04225897
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Seth Hetherington, MD
Address 0 0
ReViral Ltd
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Heather Welch, MPhil
Address 0 0
Country 0 0
Phone 0 0
+44 (0)1438 906760
Fax 0 0
Email 0 0
hwelch@reviral.co.uk
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04225897