E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Respiratory Syncytial Virus |
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E.1.1.1 | Medical condition in easily understood language |
Respiratory Syncytial Virus |
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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 |
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E.1.3 | Condition being studied is a rare disease | No |
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). |
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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. |
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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: 21-June-2019, Amendment 1 - Objective: obtaining rich serial PK blood sampling for the measurement of plasma concentrations of JNJ-53718678. |
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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. 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. |
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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.
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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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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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) and total time in the intensive care unit (ICU) (time in ICU before first dosing) -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 plasma concentration-time 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). |
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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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability and biomarkers |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 | No |
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 |
France |
Germany |
Israel |
Japan |
Korea, Republic of |
Netherlands |
Spain |
Sweden |
Switzerland |
Taiwan |
United Kingdom |
United States |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |