A Study in Infants With RSV LRTI to Evaluate RV521

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)

Sponsors

Lead Sponsor: ReViral Ltd

Source ReViral Ltd
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.

Detailed Description

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 RSV LRTI.

The clinical study consists of 3 parts, the third part (Part C) is optional:

- Part A is an open-label, multicentre, single dose study in infants hospitalised with RSV LRTI (Cohorts 1 & 2)

- Part B is a randomised, double-blind, placebo-controlled, multicentre multiple dose study in infants hospitalised with RSV LRTI (Cohorts 3, 4 & 5)

- Part C is a randomised 1:1, double-blind, placebo-controlled, multicentre, multiple-dose study in infants hospitalised with RSV LRTI I The number of subjects enrolled in Parts A and B of the study will depend on the safety and PK data from the group of subjects enrolled in specified age cohorts and the subsequent recommendation of the Data Safety Monitoring Committee (DSMC).

The DSMC may recommend a dose adjustment (either a reduction or an escalation) and/or regimen adjustment (Part B only) for subsequent subjects because of the observation of an unexpected safety/tolerability profile and/or differences between the observed and predicted exposure resulting from a specified dose of RV521.

Overall Status Recruiting
Start Date November 13, 2019
Completion Date November 2021
Primary Completion Date October 2021
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
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. 48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
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. 48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
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 48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
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 48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
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 48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
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 48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
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 48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
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 48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
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. 48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
Number of participants with changes in ECG measurements from baseline in Part A and Part B 48 hours post dose 1 (Part A) and 48 hours post dose 10 (Part B)
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. up to 48 hours post dose 10
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. up to 48 hours post dose 10
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 up to 48 hours post dose 10
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. up to 48 hours post dose 10
Secondary Outcome
Measure Time Frame
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). 48 hours post dose 1 (Part A)
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). 48 hours post dose 1 (Part A)
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). 48 hours post dose 1 (Part A)
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). 48 hours post dose 1 (Part A)
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). 48 hours post dose 1 (Part A)
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-∞). 48 hours post dose 1 (Part A)
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. 48 hours post dose 1 (Part A)
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). 48 hours post dose 1 (Part A)
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). 48 hours post dose 1 (Part A)
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. 48 hours post dose 10
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). 48 hours post dose 10
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). 48 hours post dose 10
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). 48 hours post dose 10
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). 48 hours post dose 10
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. up to 48 hours post dose 10
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. up to 48 hours post dose 10
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. 48 hours post dose 10
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. 48 hours post dose 10
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. 48 hours post dose 10
Enrollment 184
Condition
Intervention

Intervention Type: Drug

Intervention Name: RV521

Description: RV521 is an RSV F protein inhibitor administered orally

Arm Group Label: RV521

Other Name: sisunatovir

Intervention Type: Drug

Intervention Name: Placebo

Description: vehicle administered orally

Arm Group Label: Placebo

Eligibility

Criteria:

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

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.

Gender: All

Minimum Age: 1 Month

Maximum Age: 36 Months

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Seth Hetherington, MD Study Director ReViral Ltd
Overall Contact

Last Name: Heather Welch, MPhil

Phone: +44 (0)1438 906760

Email: [email protected]

Location
Facility: Status: Contact:
Reviral Site 3001 | Buenos Aires, 8000, Argentina Not yet recruiting Reviral
Reviral Site 3004 | Buenos Aires, 8000, Argentina Not yet recruiting Reviral
Reviral Site 3003 | Buenos Aires, CP1425, Argentina Not yet recruiting Reviral
Reviral Site 3005 | Ciudad Autonoma de Buenos Aires, C1431FWO, Argentina Not yet recruiting Reviral
Reviral Site 3002 | San Miguel De Tucumán, T4000, Argentina Not yet recruiting Reviral
Reviral Site 3104 | Puerto Montt, Region De Los Lagos, 5480000, Chile Not yet recruiting Reviral
Reviral Site 3106 | Los Ángeles, 4440000, Chile Not yet recruiting Reviral
Reviral Site 3101 | Osorno, 5311523, Chile Not yet recruiting Reviral
Reviral Site 3103 | Santiago, 8330024, Chile Not yet recruiting Reviral
Reviral Site 3102 | Santiago, Chile Not yet recruiting Reviral
Reviral site 3302 | Escazú, San Jose, 10203, Costa Rica Recruiting Reviral
Reviral Site 3301 | San José, 10108, Costa Rica Recruiting Reviral
Reviral Site 3303 | San José, Costa Rica Not yet recruiting Reviral
Reviral Site 3304 | San José, Costa Rica Recruiting Reviral
Reviral Site 1002 | Szeged, Csongrad, 6720, Hungary Recruiting Reviral
Reviral Site 1003 | Budapest, 1094, Hungary Recruiting Reviral
Reviral Site 1001 | Budapest, 1125, Hungary Recruiting Reviral
Reviral Site 2001 | Kota Bharu, Kelantan, 15586, Malaysia Not yet recruiting Reviral
Reviral Site 2004 | Ipoh, Perak, 30450, Malaysia Not yet recruiting Reviral
Reviral Site 2002 | Seberang Jaya, Pulau Pinang, 13700, Malaysia Not yet recruiting Reviral
Reviral Site 2003 | Kuala Terengganu, Terengganu, 20400, Malaysia Not yet recruiting Reviral
Reviral Site 2102 | Wellington, 6021, New Zealand Recruiting Reviral
Reviral Site 3203 | Chiriquí, San Pablo Viejo, Panama Recruiting Reviral
Reviral Site 3201 | Panama City, Panama Recruiting Reviral
Reviral Site 3202 | Panama City, Panama Recruiting Reviral
Reviral Site 2202 | Manila, National Capital Region, 1000, Philippines Recruiting Reviral
Reviral Site 2204 | Manila, National Capital Region, 1000, Philippines Recruiting Reviral
Reviral Site 2201 | Quezon City, National Capital Region, 1101, Philippines Recruiting Reviral
Reviral Site 2205 | Quezon City, National Capital Region, 1101, Philippines Not yet recruiting Reviral
Reviral Site 1204 | Rzeszów, Podkarpackie, 35-210, Poland Not yet recruiting Reviral
Reviral Site 1205 | Łódź, Woj. Lodzkie, 93-338, Poland Recruiting Reviral
Reviral Site 1201 | Warsaw, Woj. Mazowieckie, 02-091, Poland Recruiting Reviral
Reviral Site 1206 | Poznań, Woj. Wielkopolskie, 60-693, Poland Recruiting Reviral
Reviral Site 1203 | Kraków, Woj.Malopolskie, 30663, Poland Recruiting Reviral
Reviral Site 2302 | Hualien City, 97002, Taiwan Recruiting Reviral
Reviral Site 2303 | Kaohsiung City, 81362, Taiwan Recruiting Reviral
Reviral Site 2304 | Tainan City, 710, Taiwan Recruiting Reviral
Reviral Site 2405 | Bangkok, 10330, Thailand Not yet recruiting Reviral
Reviral Site 2401 | Bangkok, 10700, Thailand Not yet recruiting Reviral
Reviral Site 2403 | Chiang Mai, 50200, Thailand Not yet recruiting Reviral
Reviral Site 2402 | Khon Kaen, 40002, Thailand Not yet recruiting Reviral
Reviral Site 2404 | Phitsanulok, 65000, Thailand Not yet recruiting Reviral
Location Countries

Argentina

Chile

Costa Rica

Hungary

Malaysia

New Zealand

Panama

Philippines

Poland

Taiwan

Thailand

Verification Date

December 2019

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: RV521

Type: Experimental

Description: 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.

Label: Placebo

Type: Placebo Comparator

Description: 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.

Acronym REVIRAL 1
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Sequential Assignment

Intervention Model Description: 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 RSV LRTI. Due to the adaptive study design, the number of enrolled subjects may vary depending on the obtained PK and safety profiles. The clinical study consists of 3 parts: Part A is an open-label, multicentre, single dose study in infants hospitalised with RSV LRTI (Cohorts 1 & 2) Part B is a randomised, double-blind, placebo-controlled, multicentre multiple dose study in infants hospitalised with RSV LRTI (Cohorts 3, 4 & 5) Part C is a randomised 1:1, double-blind, placebo-controlled, multicentre, multiple-dose study in infants hospitalised with RSV LRTI

Primary Purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Source: ClinicalTrials.gov