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A Study of Rilematovir in Infants and Children and Subsequently in Neonates Hospitalized With Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus (RSV) (DAISY)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04583280
Recruitment Status : Not yet recruiting
First Posted : October 12, 2020
Last Update Posted : January 20, 2021
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of the study is to evaluate the efficacy of rilematovir compared to placebo treatment with respect to the clinical outcome on the RSV Recovery Scale (RRS).

Condition or disease Intervention/treatment Phase
Respiratory Tract Infections Drug: Rilematovir Drug: Rilematovir X mg/kg Drug: Placebo Phase 3

Detailed Description:
Respiratory syncytial virus (RSV), a negative-stranded ribonucleic acid (RNA) virus belonging to the Pneumoviridae family, is considered the most important cause of acute lower respiratory tract infection (LRTI) in infants and young children. In most patients, RSV results in upper respiratory tract infection (URTI) eliciting "common cold"-like symptoms, which might last up to 2 weeks, and are usually self-limiting. RSV-related LRTI is a major cause of hospital admissions and death in young children worldwide. Rilematovir is an investigational, small molecule, RSV fusion inhibitor. This study aims to evaluate the efficacy and safety of rilematovir in hospitalized infants and children (greater than or equal to [>=] 28 days to less than or equal to [<=] 5 years) and, subsequent to the completion of the substudy, in hospitalized neonates (born at term, less than [<] 28 days of age) with RSV infection. The study will include a Screening Period, a Treatment Period, and a Follow-up Period. The total study duration for each participant will be approximately 36 days (Screening included). The efficacy assessments include evaluation under the RRS and the safety assessments include evaluations of physical examinations, vital signs, electrocardiograms, clinical laboratory tests, and adverse events.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 737 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Rilematovir in Infants and Children (≥28 Days to ≤5 Years of Age) and Subsequently in Neonates (<28 Days of Age), Hospitalized With Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus (RSV)
Estimated Study Start Date : January 22, 2021
Estimated Primary Completion Date : May 6, 2024
Estimated Study Completion Date : July 30, 2024

Arm Intervention/treatment
Experimental: Rilematovir
Participants will receive rilematovir orally based on body weight and age group.
Drug: Rilematovir
Participants of age group greater than or equal to (>=) 28 days to less than (<) 3 months (age group 1) or >= 3 months to < 6 months (age group 2) or >= 6 months to less than or equal to (<=) 5 years (age group 3) will receive rilematovir orally twice a day (BID) from Days 1 to Day 7 or Day 8.
Other Name: JNJ-53718678

Drug: Rilematovir X mg/kg
Participants of age group birth at term (after at least 37 weeks of gestation) to < 28 days (age group 4) will receive rilematovir orally BID from Days 1 to Day 7 or Day 8. The dose is dependent on outcome of the substudy in neonates and following independent data monitoring (IDMC) review and recommendation.
Other Name: JNJ-53718678

Experimental: Placebo
Participants will receive matching placebo of rilematovir based on body weight and age group.
Drug: Placebo
Participant of age group 1, 2, 3 and 4 will receive matching placebo of rilematovir BID from Days 1 to Day 7 or Day 8 as per assigned age group.




Primary Outcome Measures :
  1. Respiratory Syncytial Virus (RSV) Recovery Scale (RRS) [ Time Frame: Up to Day 8 ]
    The RRS is an ordinal scale assessing a participant's clinical status.


Secondary Outcome Measures :
  1. Percentage of Participants with Clinically Resolved RSV Disease as Assessed by ClinRO Sign/Symptoms Questionnaire [ Time Frame: Up to Day 8 ]
    Clinical resolution is defined by free of oxygen supplementation, and free of supplemental feeding, and no medical need for intensive care unit (ICU), and key RSV Signs/Symptoms resolved to absent or mild as per the Pediatric RSV Electronic Severity and Outcome Rating Scale (PRESORS) Clinician Rated Outcome (ClinRO) Signs/Symptoms questionnaire.

  2. Time From First Study Dose to Resolution of key RSV Signs/Symptoms Based on ObsRO [ Time Frame: Up to Day 21 ]
    Time from first study dose to resolution of key RSV Signs/symptoms (absent or mild) will be assessed based on parent's/caregiver's PRESORS Observer Rated Outcome (ObsRO) signs/symptoms and supplementation free (oxygen and feeding/hydration).

  3. Time From Discharge to Resolution of key RSV Signs/Symptoms based on ObsRO Sign/Symptoms Questionnaire [ Time Frame: Up to Day 21 ]
    Time from discharge to resolution of key RSV Signs/symptoms will be assessed based on PRESORS ObsRO Sign/Symptoms (only including participants who did not reach resolution before first discharge).

  4. Time From First Dosing to end of Oxygen Supplementation [ Time Frame: Up to Day 35 ]
    Time from first dosing to end of oxygen supplementation will be assessed (only including participants who were receiving oxygen supplementation at the time of first dosing).

  5. Number of Participants with Post-baseline RSV-Related Complications [ Time Frame: Up to Day 35 ]
    Number of participants with post-baseline RSV-related complications will be assessed.

  6. Number of Participants with Adverse Events [ Time Frame: Up to Day 35 ]
    An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product.

  7. Number of Participants with Abnormalities in Clinical Laboratory Values [ Time Frame: Up to Day 35 ]
    Number of participants with abnormalities in Clinical laboratory values (Hematology, Clinical chemistry, and routine urinalysis) will be assessed.

  8. Number of Participants with Abnormalities in Electrocardiograms (ECG) [ Time Frame: Up to Day 35 ]
    Number of participants with ECG abnormalities will be assessed.

  9. Number of Participants with Abnormalities in Vital Signs [ Time Frame: Up to Day 35 ]
    Number of participants with vital signs (Temperature, pulse/heart rate, and peripheral capillary oxygen saturation [SpO2]) abnormalities will be assessed.

  10. Time to Resolution of Signs/symptoms of RSV Disease as Assessed by ObsRO Signs/Symptoms Questionnaire [ Time Frame: Up to Day 21 ]
    Time to resolution of signs/symptoms (absent or mild) of RSV disease as assessed by PRESORS ObsRO signs/symptoms questionnaire.

  11. PRESORS ObsRO Signs/Symptoms Questionnaire Scores [ Time Frame: Up to Day 21 ]
    PRESORS ObsRO Signs/Symptoms Questionnaire Scores will be assessed. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease.

  12. Change From Baseline in PRESORS ObsRO Signs/Symptoms Questionnaire Scores Over Time [ Time Frame: Baseline up to Day 21 ]
    Change from baseline in PRESORS ObsRO Signs/Symptoms questionnaire scores over time will be assessed. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease.

  13. Time to Improvement in ObsRO General Health Questions (GHQ) [ Time Frame: Up to Day 21 ]
    Time to improvement on PRESORS ObsRO GHQ will be assessed. ObsRO GHQ contains questions which are used to record the caregiver's general impression of the child's RSV disease severity, change in RSV disease severity, and overall health status.

  14. Time to resolution of Signs/Symptoms of RSV Disease as Assessed by ClinRO Signs/Symptoms Questionnaire [ Time Frame: Up to Day 21 ]
    Time to resolution of signs/symptoms of RSV disease as assessed by ClinRO signs/symptoms questionnaire will be reported.

  15. PRESORS ClinRO Signs/Symptoms Questionnaire Scores [ Time Frame: Up to Day 21 ]
    PRESORS ClinRO signs/symptoms questionnaire score will be reported. PRESORS is a questionnaire recording presence and severity of signs and symptoms of RSV disease.

  16. Change From Baseline in ClinRO Signs/Symptoms Questionnaire Scores [ Time Frame: Baseline up to Day 21 ]
    Change from baseline in PRESORS ClinRO signs/symptoms questionnaire scores over time will be assessed.

  17. Percentage of Participants with Clinically Resolved RSV Disease Based on ClinRO Signs/symptoms [ Time Frame: Day 2 to 8 ]
    Percentage of participants with clinically resolved RSV disease based on PRESORS ClinRO signs/symptoms will be assessed.

  18. Change from Baseline in ClinRO GHQ Score Over Time [ Time Frame: Baseline up to Day 21 ]
    Change from baseline in ClinRO GHQ score over time will be assessed. ClinRO GHQ contains questions which are used to record the caregiver's general impression of the child's RSV disease severity, change in RSV disease severity, and overall health status.

  19. Time to Hospital Discharge From Start of Dosing [ Time Frame: Up to Day 35 ]
    Time to hospital discharge from start of dosing will be assessed.

  20. Time to Readiness for Hospital Discharge [ Time Frame: Up to Day 35 ]
    Time to readiness of participants for hospital discharge (as evaluated by the investigator) will be assessed.

  21. Percentage of Participants Requiring Intensive Care Unit (ICU) Stay [ Time Frame: Up to Day 35 ]
    Percentage of participants requiring ICU stay will be assessed.

  22. Duration of Requiring ICU Stay [ Time Frame: Up to Day 35 ]
    Duration of requiring ICU stay will be assessed.

  23. Percentage of Participants Requiring Re-hospitalization for Respiratory/other Reasons [ Time Frame: Up to Day 35 ]
    Percentage of participants requiring re-hospitalization for respiratory/other reasons will be assessed.

  24. Time to end of Oxygen Supplementation [ Time Frame: Up to Day 35 ]
    Time to end of oxygen supplementation will be assessed.

  25. Percentage of Participants Requiring Oxygen Supplementation [ Time Frame: Up to Day 35 ]
    Percentage of participants requiring oxygen supplementation will be assessed.

  26. Duration of Oxygen Supplementation [ Time Frame: Up to Day 35 ]
    Duration of oxygen supplementation will be assessed.

  27. Time to end of Supplemental Feeding/hydration [ Time Frame: Up to Day 35 ]
    Time to end of supplemental feeding/hydration will be assessed.

  28. Percentage of Participants Requiring Hydration and/or Feeding by Intravenous (IV) Administration or Nasogastric Tube [ Time Frame: Up to Day 35 ]
    Percentage of participants requiring hydration and/or feeding by IV administration or nasogastric tube will be assessed.

  29. Duration of Supplemental Feeding/hydration [ Time Frame: Up to Day 35 ]
    Duration of supplemental feeding/hydration will be assessed.

  30. Time to end of Supplemental Oxygen and/or Feeding/hydration [ Time Frame: Up to Day 35 ]
    Time to end of supplemental oxygen and/or feeding/hydration will be assessed.

  31. Number of Participants with Medical Encounters and Treatments [ Time Frame: Up to Day 35 ]
    Number of participants with medical care encounters and treatments (including physician or emergency room visits, tests and procedures, and medications, surgeries and other procedures) will be reported.

  32. Number of Participants with Antibiotic Treatment Episodes [ Time Frame: Up to Day 35 ]
    Number of participants with antibiotic treatment episodes will be assessed.

  33. Number of Participants with Systemic or Inhaled Corticosteroids and Bronchodilators use [ Time Frame: Up to Day 35 ]
    Number of participants with systemic or inhaled corticosteroids and bronchodilators use will be assessed.

  34. RSV Viral Load Area Under the RSV Viral Load-time Curve [AUC]) From Immediately Prior to First Dose of Study Intervention (Baseline) Through Day 3, Day 5, and Day 8 [ Time Frame: Baseline, Day 3, 5 and Day 8 ]
    RSV viral load area under the RSV viral load-time curve [AUC] will be assessed by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) assay of nasal swabs.

  35. RSV Viral Load Over Time [ Time Frame: From Baseline to Day 21 ]
    RSV viral load over time will be assessed by qRT-PCR assay in the mid-turbinate nasal swab specimens.

  36. Change From Baseline in RSV Viral Load Over Time [ Time Frame: Baseline to Day 21 ]
    Change From baseline in RSV viral load over time will be assessed by qRT-PCR assay in the mid-turbinate nasal swabs specimens.

  37. Percentage of Participants with Undetectable RSV Viral Load [ Time Frame: Up to Day 21 ]
    Percentage of participants with undetectable RSV viral load will be assessed.

  38. Number of Participants with Post-baseline Changes in the RSV F-gene Compared with Baseline Sequences [ Time Frame: Up to Day 21 ]
    Number of participants with post-baseline changes in the RSV F-gene compared with baseline sequences will be assessed.

  39. Plasma Concentration of Rilematovir [ Time Frame: Post-dose (Day 1) and pre-dose (Day 2) ]
    Plasma concentration of rilematovir will be assessed.

  40. Acceptability and Palatability of the Rilematovir Formulation as Assessed by Parent(s)/Caregiver(s) [ Time Frame: Day 8 ]
    Acceptability and palatability of the rilematovir formulation will be assessed through a questionnaire completed by parent(s)/caregiver(s).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • The participant weighs within greater than or equal to (>=) 2.4 kilograms (kg) and less than or equal to (<=) 24.6 kg
  • Each participant's parent(s) (preferably both if available or as per local requirements) or their legally acceptable representative(s) has/have signed an informed consent form (ICF) indicating that (s)he understands the purpose of, and procedures required for, the study; is willing for their child to participate in the study; with regards to the concomitant medication, the lifestyle consideration and study procedures and assessments to be performed by the parent(s)/caregiver(s) as well as those by the investigator/study site personnel
  • The participant has an acute respiratory illness with at least 1 of the signs/symptoms within 24 hours prior to start of screening and at screening, as evaluated by the investigator in Upper respiratory tract infection: nasal congestion or rhinorrhea; and Lower respiratory tract infection: increased respiratory effort (as evidenced by subcostal, intercostal or tracheosternal retractions, grunting, head bobbing, nasal flaring, or tachypnea), wheezing, cough, cyanosis, or apnea; and systemic/general: feeding difficulties (defined as <75 percent [%] intake of normal food amounts); dehydration; fever; disturbed sleep, or disturbed activity level (irritable/restless/agitated/less responsive)
  • The time of onset of RSV signs/symptoms to the anticipated time of randomization must be less than or equal to (<=) 3 days. Onset of signs/symptoms is defined as the time of the day (or part of the day if time of the day cannot be specified) the parent(s)/caregiver(s) became aware of the first sign and/or symptom consistent with respiratory or systemic/general manifestation of signs/symptoms of RSV infection. The time of sign/symptom onset has to be assessed as accurately as possible
  • Participants are otherwise healthy or have (a) risk factor(s) for severe RSV disease

Exclusion criteria:

  • The participant has had either confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (test positive) during the four weeks prior to randomization, or close contact with a person with COVID-19 (test confirmed or suspected SARS CoV-2 infection) within 14 days prior to randomization
  • Confirmed QT interval corrected for heart rate according to Fridericia's formula (QTcF) interval greater than (>) 450 milliseconds (msec) per the machine read parameter result at screening. Presence of an abnormal QTcF interval should be confirmed by repeat electrocardiogram (ECG) recording during screening
  • Known personal or family history of Long QT Syndrome or sudden cardiac death
  • Presence of repetitive ventricular premature contractions (>10/minutes [min]), second- or third-degree heart block, or complete or incomplete left bundle branch block, or complete right bundle branch block per the machine read ECG result at screening. Presence of any of the above abnormalities should be confirmed by repeat ECG recording during screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04583280


Contacts
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Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

Locations
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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT04583280    
Other Study ID Numbers: CR108899
2020-002023-11 ( EudraCT Number )
53718678RSV3001 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: October 12, 2020    Key Record Dates
Last Update Posted: January 20, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
URL: https://www.janssen.com/clinical-trials/transparency

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Respiratory Tract Infections
Respiratory Tract Diseases