Clinical Trials Register

Summary
EudraCT Number:	2019-001551-39
Sponsor's Protocol Code Number:	53718678RSV2005
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-08-20
Trial results	View 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

Germany - BfArM

A.2

EudraCT number

2019-001551-39

A.3

Full title of the trial

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Clinical Outcomes, Antiviral Activity, Safety, Tolerability, Pharmacokinetics, and Pharmacokinetics/Pharmacodynamics of JNJ-53718678 in Adult and Adolescent Hematopoietic Stem Cell Transplant Recipients with Respiratory Syncytial Virus Infection of the Upper Respiratory Tract

A.3.1

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

Effects of JNJ-53718678 in Adult and Adolescent Patients Who had a Hematopoietic Stem Cell Transplantation and Who are Infected With RSV

A.3.2

Name or abbreviated title of the trial where available

FREESIA

A.4.1

Sponsor's protocol code number

53718678RSV2005

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

P/030/2021

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Janssen Sciences Ireland UC
B.1.3.4	Country	Belgium
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	Janssen Sciences Ireland UC
B.4.2	Country	Ireland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen-Cilag International N.V.
B.5.2	Functional name of contact point	Clinical Registry Group
B.5.3	Address:
B.5.3.1	Street Address	Archimedesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31 715242166
B.5.5	Fax number	+31 715242110
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.com

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.3.1	Product name	JNJ-53718678
D.3.2	Product code	JNJ-53718678
D.3.4	Pharmaceutical form	Powder and solvent for oral suspension
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	rilematovir
D.3.9.2	Current sponsor code	JNJ-53718678
D.3.9.4	EV Substance Code	SUB166668
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
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.IMP: 2
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.3.1	Product name	rilematovir
D.3.2	Product code	JNJ-53718678
D.3.4	Pharmaceutical form	Film-coated tablet
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	rilematovir
D.3.9.2	Current sponsor code	JNJ-53718678
D.3.9.4	EV Substance Code	SUB166668
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	125
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	Powder and solvent for oral suspension
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
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

Respiratory Syncytial Virus

E.1.1.1

Medical condition in easily understood language

Respiratory Syncytial Virus

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	HLT
E.1.2	Classification code	10038717
E.1.2	Term	Respiratory syncytial viral infections
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to evaluate the effect of JNJ-53718678 on the development of RSV lower tract respiratory infections (LRTIs) in adult hematopoietic stem cell transplant (HSCT) recipients with RSV upper respiratory tract infection (URTI).

E.2.2

Secondary objectives of the trial

To evaluate:
1. The effect of JNJ-53718678 on the development of RSV-associated lower respiratory tract complications (LRTC) in adult and adolescent HSCT recipients with RSV URTI.
2. The safety and tolerability of JNJ-53718678.
3. The impact of JNJ-53718678 on progression to respiratory failure and on all-cause mortality.
4. The impact of JNJ-53718678 on the clinical course of RSV infection.
5. The PK of JNJ-53718678.
6. The relationship between the PK of JNJ-53718678 and the PD after repeated dosing of JNJ-53718678.
7. The antiviral effect of JNJ-53718678 as measured by RSV viral load in bilateral mid-turbinate nasal swab samples by quantitative reverse transcription polymerase chain reaction (qRT PCR) assay.
8. The impact of RSV and its treatment on health-related quality of life (HRQOL).
9. The emergence of mutations in the viral genome potentially associated with resistance to JNJ-53718678.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Clinical Outcomes, Antiviral Activity, Safety, Tolerability, Pharmacokinetics, and Pharmacokinetics/Pharmacodynamics of JNJ-53718678 in Adult and Adolescent Hematopoietic Stem Cell Transplant Recipients with Respiratory Syncytial Virus Infection of the Upper Respiratory Tract
- Date & Version: 11-May-2021, Amendment 6/DEU-2
- Objective: obtaining rich serial PK blood sampling for the measurement of plasma concentrations of JNJ-53718678.

E.3

Principal inclusion criteria

Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1. Male or female.
2. 18 to 75 years of age, inclusive. Subjects ≥13 and <18 years of age may be enrolled in selected countries and study sites consistent with local regulations. Note: Adolescent participants will not be included in the study in Germany.
3. Received an autologous or allogeneic HSCT using any conditioning regimen.
4. ALC <1,000 cells/µL. The local assessment confirming ALC <1,000 cells/µL should be performed no more than 48 hours prior to randomization.
5. The participant has been diagnosed with RSV infection using a rapid PCR- or other molecular-based diagnostic assay performed on a bilateral mid-turbinate nasal swab sample as part of the study-specific screening assessment or on an upper respiratory tract sample as part of SOC testing.
6. New onset of at least 1 of the following respiratory symptoms within 4 days prior to the anticipated start of dosing (Day 1): nasal congestion, rhinorrhea, cough or pharyngitis (sore throat), and/or worsening of one of these chronic (associated with previously existing diagnosis, eg, chronic rhinorrhea, seasonal allergies, chronic lung disease) respiratory symptoms within 4 days prior to the anticipated start of dosing (Day 1).
7. No evidence of new abnormalities consistent with LRTI on a chest X-ray relative to the most recent chest X-ray, as determined by the local radiologist (preferentially) or the investigator. A chest X-ray should be performed no more than 48 hours prior to randomization. If a chest X-ray has not been obtained as part of SOC, it must be obtained during Screening.

E.4

Principal exclusion criteria

Any potential participant who meets any of the following criteria will be excluded from participating in the study:
1. Admitted to the hospital primarily for a lower respiratory tract disease of any cause as determined by the investigator.
2. Requires supplemental oxygen at Screening or any time between Screening and randomization.
3. Documented to be positive for other respiratory viruses (limited to influenza, parainfluenza, human rhinovirus, adenovirus, human metapneumovirus, or coronavirus) within 7 days prior to or at the Screening visit, if determined by local SOC testing (additional testing is not required).
4. Clinically significant bacteremia or fungemia within 7 days prior to or at Screening that has not been adequately treated, as determined by the investigator.
5. Known allergies, hypersensitivity, or intolerance to JNJ-53718678 or its excipients.
6. Bacterial, fungal, or viral pneumonia within 2 weeks prior to Screening that has not been adequately treated, as determined by the investigator.
7. Criterion modified per Amendment 2/DEU-1.
7.1 Criterion modified per Amendment 3.
7.2 Confirmed QTcF interval >450 milliseconds per the machine read parameter result at Screening. Presence of an abnormal QTcF interval should be confirmed by repeat ECG recording during Screening.
8. Criterion modified per Amendment 2/DEU-1.
8.1 Criterion modified per Amendment 5
8.2 Clinically significant abnormal ECG findings (other than QTcF interval >450 milliseconds, see exclusion criterion 7.2) not consistent with the underlying condition in the study population, as judged by the investigator based on the machine read ECG results at Screening.
9. Has evidence of one of the following ECG abnormalities per the machine read ECG results at Screening confirmed by repeat ECG recording:
- Repetitive premature ventricular contractions (>10/min)
- Second- or third-degree heart block
- Complete or incomplete left bundle branch block or complete right bundle branch block

E.5 End points

E.5.1

Primary end point(s)

The proportion of participants who develop RSV LRTI per the Endpoint Adjudication Committee (EAC)’s assessment through Visit Day 28.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 28

E.5.2

Secondary end point(s)

1. The proportion of participants who develop RSV-associated LRTC per the EAC’s assessment through Visit Day 28.
2. Safety and tolerability, as assessed by AEs, clinical laboratory testing, ECGs, vital signs, throughout the study.
3. The proportion of participants progressing to respiratory failure and all-cause mortality.
4. Clinical course-related endpoints:
-Number of supplemental O2 free days through Day 28
-Incidence of O2 requirement, total length and type (eg, supplemental oxygen, noninvasive pressure ventilation, invasive mechanical ventilation [tracheal tube, laryngeal mask, or tracheostomy])
-Respiratory rate, heart rate, body temperature, and peripheral capillary oxygen saturation (SpO2) over time as measured by the investigator during scheduled visits
-Proportion of participants hospitalized (of participants who were not hospitalized at baseline), proportion of participants re-hospitalized (of participants who were hospitalized at baseline and discharged during the study and of participants who were not hospitalized at baseline, required hospitalization, and were discharged during the study)
-Total length of hospital stay (time in hospital before first dosing is discarded) and total time in the intensive care unit (ICU) (time in ICU before first dosing is discarded)
-Incidence of Grade 3 and Grade 4 adverse events (AEs) in the Infections and Infestations System Organ Class
-Incidence of respiratory and thoracic-related AEs
-Incidence of antibiotic use in participants who develop and in those who do not develop RSV LRTI or RSV-associated LRTC per the EAC’s assessment
-Time to resolution of symptoms, assessed through an instrument for patient-reported symptoms (Respiratory Infection Intensity and Impact Questionnaire [RiiQ] Symptom Scale)
-Change from baseline through Day 28 in severity of symptoms reported by subjects in the RiiQ Symptom Scale
-Time to resolution of respiratory illness, through the Patient Global Impression of Severity (PGI-S) Scale
-Change in Patient Global Impression of Health (PGI-H) and Patient Global Impression of Change (PGI-C) Scales through Day 28
5. PK parameters of JNJ-53718678
6. PK/PD analysis of plasma concentration-time data of JNJ-53718678 using (non)-linear mixed-effects modeling.
7. Virologic parameters derived from the RSV viral load as measured by a qRT-PCR assay in bilateral mid-turbinate nasal swab samples including:
- RSV viral load and change from baseline over time.
- RSV viral load AUC from immediately prior to first dose of study intervention.
- time to undetectable RSV viral load.
- proportion of participants with undetectable RSV viral load at each time point throughout the study.
8. Change from baseline for the HRQOL through Day 28 (as assessed through the 5-level EuroQol 5-Dimension [EQ-5D-5L] and RiiQ Impact Scales].
9. Changes from baseline in the RSV F gene sequence (and potentially other regions of the RSV genome, at the discretion of the sponsor's virologist).

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Through Visit Day 28
2. Throughout the study
3. Throughout the study
4. Throughout the study
5. D1, D3 ±1, D8 ±1, D15 ±1, D22
6. Throughout the study (depending on PK modeling)
7.
- Baseline
- Baseline through Day 8, Day 11, Day 15, Day 22, and Day 28
- During visits
- During visits
8. Screening, pre-dose, D3±1, D5±1, D8±1, D11±1, D15±1, D22, D28±3
9. pre-dose, D3±1, D5±1, D8±1, D11±1, D15±1, D22, D28±3, D35±3

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

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

Yes

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability and biomarkers

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

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

Australia

Argentina

Belgium

Brazil

Bulgaria

Canada

Germany

Israel

Italy

Japan

Korea, Republic of

Malaysia

Netherlands

Russian Federation

Spain

Sweden

Switzerland

Taiwan

United Kingdom

United States

France

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

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:

200

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

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

249

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)

Standard of care

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

2020-09-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-12-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-02-04

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