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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04225897




Registration number
NCT04225897
Ethics application status
Date submitted
11/12/2019
Date registered
13/01/2020
Date last updated
26/06/2023

Titles & IDs
Public title
A Study to Learn About the Effects of Sisunatovir in Infants With Respiratory Syncytial Virus Lower Respiratory Tract Infection.
Scientific title
A Phase 2 Open-Label Study in Infants With REspiratory Syncytial VIRus Lower RespirAtory Tract Infection, Followed by a DoubLe-blind, Placebocontrolled Part, to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Effect of RV521 (REVIRAL 1)
Secondary ID [1] 0 0
C5241003
Secondary ID [2] 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
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections
Respiratory 0 0 0 0
Other respiratory disorders / diseases

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 suspending diluent prior to oral administration on a mg/kg basis. Instructions for opening the capsule(s) and dispersing the contents in a fixed volume of suspending diluent 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 suspending diluent and given orally BID. Instructions for opening the capsule(s) and dispersing the contents in a fixed volume of suspending diluent 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.
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.
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
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
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
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
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
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
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.
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
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.
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.
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
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.
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).
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).
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).
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).
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).
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).
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.
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).
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).
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.
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).
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).
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).
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).
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.
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.
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.
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.
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.
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
Sex
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
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/11/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/12/2022
Sample size
Target
Accrual to date
Final
51
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
Caba
Country [3] 0 0
Canada
State/province [3] 0 0
Alberta
Country [4] 0 0
Chile
State/province [4] 0 0
Metropolitana
Country [5] 0 0
Chile
State/province [5] 0 0
Region DE LOS Lagos
Country [6] 0 0
Costa Rica
State/province [6] 0 0
San Jose
Country [7] 0 0
Hungary
State/province [7] 0 0
Budapest
Country [8] 0 0
Hungary
State/province [8] 0 0
Kaposvar
Country [9] 0 0
Israel
State/province [9] 0 0
Beer-Sheva
Country [10] 0 0
Israel
State/province [10] 0 0
Haifa
Country [11] 0 0
Israel
State/province [11] 0 0
Petach Tikava
Country [12] 0 0
Korea, Republic of
State/province [12] 0 0
Seoul
Country [13] 0 0
Malaysia
State/province [13] 0 0
Kelantan
Country [14] 0 0
Malaysia
State/province [14] 0 0
Perak
Country [15] 0 0
Malaysia
State/province [15] 0 0
Pulau Pinang
Country [16] 0 0
Malaysia
State/province [16] 0 0
Sarawak
Country [17] 0 0
Malaysia
State/province [17] 0 0
Terengganu
Country [18] 0 0
Malaysia
State/province [18] 0 0
Parek
Country [19] 0 0
New Zealand
State/province [19] 0 0
Wellington
Country [20] 0 0
Panama
State/province [20] 0 0
Panama
Country [21] 0 0
Poland
State/province [21] 0 0
Krakow
Country [22] 0 0
Poland
State/province [22] 0 0
Lodz
Country [23] 0 0
Poland
State/province [23] 0 0
Warszawa
Country [24] 0 0
Spain
State/province [24] 0 0
Barcelona
Country [25] 0 0
Spain
State/province [25] 0 0
Madrid
Country [26] 0 0
Spain
State/province [26] 0 0
Pamplona
Country [27] 0 0
Spain
State/province [27] 0 0
Santiago de Compostela
Country [28] 0 0
Taiwan
State/province [28] 0 0
Hsinchu City
Country [29] 0 0
Taiwan
State/province [29] 0 0
Hualien
Country [30] 0 0
Taiwan
State/province [30] 0 0
Kaohsiung City
Country [31] 0 0
Taiwan
State/province [31] 0 0
Tainan City
Country [32] 0 0
Thailand
State/province [32] 0 0
Bangkok
Country [33] 0 0
Thailand
State/province [33] 0 0
Chiang Mai
Country [34] 0 0
Thailand
State/province [34] 0 0
Chiangrai
Country [35] 0 0
Thailand
State/province [35] 0 0
khon Kaen
Country [36] 0 0
Thailand
State/province [36] 0 0
Khon Kaen
Country [37] 0 0
Thailand
State/province [37] 0 0
Phitsanulok
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Liverpool
Country [39] 0 0
United Kingdom
State/province [39] 0 0
London
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Southampton

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this clinical trial is to learn about the safety and effects of the study
medicine (sisunatovir). Sisunatovir is developed as potential treatment of Respiratory
Syncytial Virus (RSV) infections. This study will assess sisunatovir as compared to placebo
in infants aged 1 month to 36 months who are hospitalized with RSV lower respiratory tract
infection (LRTI). A placebo looks like the study medicine but does not contain any active
medicine in it.

This study will be conducted in 3 parts:

In Part A participants aged 6 months to 3 years will be given a single dose of 2.5 mg/kg of
sisunatovir in Cohort 1. In Cohort 2, participants age 1 month to 6 months will receive a
single dose of 2 mg/kg of sisunatovir only after the completion of Cohort 1. 12-24
participants will be enrolled in Part A In Part B participants age 1 month to 36 months will
receive sisunatovir or placebo dosed every 12 hours for 5 days. Doses for part B will be
determined after the completion of Part A. 24-40 participants will be enrolled in Part B.

The dose regimen for Part C will be determined after the completion of Part B. Approximately
120 participants age 1 month to 36 months will receive either sisunatovir or placebo.

To participate in this study participants must meet the following criteria:

1. Age 1 month to 36 months

2. Weight = 3.5 kg

3. Diagnosis of LRTI

4. Diagnosis of RSV

5. Hospitalization due to RSV LRTI
Trial website
https://clinicaltrials.gov/ct2/show/NCT04225897
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04225897