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

• Register: EUCTR
• Last refreshed on: 15 November 2021
• Main ID: EUCTR2019-001551-39-BE
• Date of registration: 03/10/2019
• Prospective Registration: Yes
• Primary sponsor: Janssen Sciences Ireland UC
• Public title: Effects of JNJ-53718678 in Adult and Adolescent Patients Who had a Hematopoietic Stem Cell Transplantation and Who are Infected With RSV
• Scientific 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 - FREESIA
• Date of first enrolment: 11/10/2019
• Target sample size: 249
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-001551-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, France, Germany, Israel, Italy, Japan, Korea, Republic of, Malaysia, Netherlands, Russian Federation, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International N.V.

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International N.V.

Key inclusion & exclusion criteria

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.
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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 5
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 44

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 3:
7.1 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 5:
8.1 Clinically significant abnormal ECG findings (other than QTcF interval >450 milliseconds, see exclusion criterion 7) 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: 1) Repetitive premature ventricular contractions (>10/min.); 2) Second- or third- degree heart block; 3) Complete or incomplete left bundle branch block or complete right bundle branch block






Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Respiratory Syncytial Virus
MedDRA version: 20.0 Level: HLT Classification code 10038717 Term: Respiratory syncytial viral infections System Organ Class: 100000004862

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Product Name: JNJ-53718678
Product Code: JNJ-53718678
Pharmaceutical Form: Powder and solvent for oral suspension
INN or Proposed INN: rilematovir
Current Sponsor code: JNJ-53718678
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Powder and solvent for oral suspension
Route of administration of the placebo: Oral use

Product Name: rilematovir
Product Code: JNJ-53718678
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: rilematovir
Current Sponsor code: JNJ-53718678
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: 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.

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

Main Objective: 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).

Timepoint(s) of evaluation of this end point: Day 28

Secondary Outcome(s)

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

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 area under the curve (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).

Secondary ID(s)

53718678RSV2005

2019-001551-39-FR

Source(s) of Monetary Support

Janssen Sciences Ireland UC

Ethics review

Status: Approved
Approval date: 11/10/2019
Contact: