Clinical Trials Register

Summary
EudraCT Number:	2019-003746-33
Sponsor's Protocol Code Number:	REVC006
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-05-20
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2019-003746-33

A.3

Full title of the trial

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)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.4.1

Sponsor's protocol code number

REVC006

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ReViral Ltd.
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	ReViral
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ReViral Ltd.
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	Stevenage Bioscience Catalyst, Gunnels Wood Road
B.5.3.2	Town/ city	Stevenage
B.5.3.3	Post code	SG1 2FX
B.5.3.4	Country	United Kingdom
B.5.6	E-mail	hwelch@reviral.co.uk

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	RV521
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sisunatovir
D.3.9.2	Current sponsor code	RV521 Hydrochloride, RV521.HCl
D.3.9.3	Other descriptive name	RV521
D.3.9.4	EV Substance Code	SUB184917
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

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.

E.1.1.1

Medical condition in easily understood language

respiratory infection

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10035732
E.1.2	Term	Pneumonia respiratory syncytial viral
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	HLGT
E.1.2	Classification code	10024970
E.1.2	Term	Respiratory tract infections
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10024968
E.1.2	Term	Lower respiratory tract infection
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10065188
E.1.2	Term	Lower respiratory tract infection viral
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

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.

E.2.3

Trial contains a sub-study

E.3

Principal 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

E.4

Principal 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.

E.5 End points

E.5.1

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

E.5.1.1

Timepoint(s) of evaluation of this end point

1 Pre-dose baseline (Day 1) through Visit 8 (Day 28)
2 Pre-dose baseline (Day 1)
through study completion; up to Visit 8 (Day 28)

E.5.2

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 hospitalization during the study [ Time
20 Proportion of subjects requiring ICU
21 Mean number of days in ICU
22 Proportion of subjects requiring mechanical ventilation
23 Number of subjects who experience death (all-cause mortality)
24 Number of subjects who experience death attributable to LRTC

E.5.2.1

Timepoint(s) of evaluation of this end point

End points 1, 23-24 : First
dose of study drug through Visit 8 (Day 28)
End points 2-6, 17-22 : Baseline (Day 1)
through Visit 8 (Day 28)
End point 7: Collected at Visit 2/Day 1 (pre-dose), Visit 4/Day 3, Visit 6/Day 14 and Visit 8/Day 28
End points 8: 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)
End points 9-10: Pre-dose baseline (Day 1) and every visit
through Visit 8 (Day 28)
End points 11-13: Pre-dose baseline
(Day 1) through study completion; up to Visit 8 (Day 28)
End points 14-15: Daily from baseline (Day
1) through Visit 8 (Day 28)
End points 23-24: First dose
of study drug through Visit 8 (Day 28)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Australia

Belgium

Brazil

Canada

Chile

France

Israel

Italy

Korea, Democratic People's Republic of

Malaysia

Spain

Taiwan

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS (31 May 2023)

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

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:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

Information not present in EudraCT

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

200

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

The treatment of the subject after the participation in the study is N/A

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-09-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-07-07

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2021-12-07

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