Clinical Trial Results:
A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Orally Administered Lumicitabine (JNJ-64041575) Regimens in Hospitalized Infants and Children Aged 28 Days to 36 Months Infected With Respiratory Syncytial Virus
Summary
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EudraCT number |
2017-001862-56 |
Trial protocol |
GB DE BE FI SK ES IE PT FR IT |
Global end of trial date |
23 Mar 2018
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Results information
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Results version number |
v1 |
This version publication date |
26 Apr 2019
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First version publication date |
26 Apr 2019
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
64041575RSV2004
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03333317 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Janssen- Cilag International NV
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Sponsor organisation address |
Turnhoutseweg 30, Beerse, Belgium, B-2340
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Public contact |
Clinical Registry Group, Janssen- Cilag International NV, ClinicalTrialsEU@its.jnj.com
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Scientific contact |
Clinical Registry Group, Janssen- Cilag International NV, ClinicalTrialsEU@its.jnj.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001758-PIP01-15 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
23 Mar 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
23 Mar 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Mar 2018
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The purpose of this study was to determine in hospitalized infants and children who were infected with respiratory syncytial virus (RSV) the dose-response relationship of multiple regimens of lumicitabine on antiviral activity based on nasal RSV shedding using quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR).
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Protection of trial subjects |
The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements. Safety evaluations were based upon the type, incidence, and severity of treatment-emergent adverse events (TEAEs) and adverse events (AEs) of special interest reported throughout the study, and on changes in vital sign measurements, clinical laboratory test results, physical examinations and 12-lead electrocardiograms (ECGs).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
24 Nov 2017
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
2 Years | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Japan: 7
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Worldwide total number of subjects |
7
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
6
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Children (2-11 years) |
1
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||
Pre-assignment
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Screening details |
Total 8 subjects that met all the eligibility criteria and had signed an ICF were enrolled, of which 7 subjects were randomized to receive lumicitabine or placebo. One eligible subject was not randomized and treated due to a lack of availability of study drug at the clinical site. | ||||||||||||
Period 1
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Period 1 title |
Treatment and Follow-up (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer | ||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||
Arm description |
Subjects received a single dose of lumicitabine-40 milligrams/kilogram (mg/kg) matched placebo as a loading dose (LD) (Dose 1) followed by 9 maintenance dose (MD) of lumicitabine-20 mg/kg matched placebo twice a day or a single dose of lumicitabine-60 mg/kg matched placebo LD (Dose 1) followed by nine lumicitabine-40 mg/kg matched placebo MD (Dose 2 to 10). | ||||||||||||
Arm type |
Placebo Comparator | ||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received oral administration of matching placebo.
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Arm title
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Lumicitabine 40/20 mg/kg LD/MD | ||||||||||||
Arm description |
Subjects received a single dose of lumicitabine-40 mg/kg as LD (Dose 1) followed by 9 MD doses of lumicitabine 20 mg/kg twice a day. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Lumicitabine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received a single dose of lumicitabine-40mg/kg as LD (Dose 1) followed by 9 MD doses of lumicitabine-20 mg/kg twice a day.
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Arm title
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Lumicitabine 60/40 mg/kg LD/MD | ||||||||||||
Arm description |
Subjects received a single dose of lumicitabine-60 mg/kg as LD (Dose 1) followed by 9 MD doses of lumicitabine 40 mg/kg twice a day. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Lumicitabine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received a single dose of lumicitabine-60mg/kg as LD (Dose 1) followed by 9 MD doses of lumicitabine-40mg/kg twice a day.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Subjects received a single dose of lumicitabine-40 milligrams/kilogram (mg/kg) matched placebo as a loading dose (LD) (Dose 1) followed by 9 maintenance dose (MD) of lumicitabine-20 mg/kg matched placebo twice a day or a single dose of lumicitabine-60 mg/kg matched placebo LD (Dose 1) followed by nine lumicitabine-40 mg/kg matched placebo MD (Dose 2 to 10). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lumicitabine 40/20 mg/kg LD/MD
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Reporting group description |
Subjects received a single dose of lumicitabine-40 mg/kg as LD (Dose 1) followed by 9 MD doses of lumicitabine 20 mg/kg twice a day. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lumicitabine 60/40 mg/kg LD/MD
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Reporting group description |
Subjects received a single dose of lumicitabine-60 mg/kg as LD (Dose 1) followed by 9 MD doses of lumicitabine 40 mg/kg twice a day. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Subjects received a single dose of lumicitabine-40 milligrams/kilogram (mg/kg) matched placebo as a loading dose (LD) (Dose 1) followed by 9 maintenance dose (MD) of lumicitabine-20 mg/kg matched placebo twice a day or a single dose of lumicitabine-60 mg/kg matched placebo LD (Dose 1) followed by nine lumicitabine-40 mg/kg matched placebo MD (Dose 2 to 10). | ||
Reporting group title |
Lumicitabine 40/20 mg/kg LD/MD
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Reporting group description |
Subjects received a single dose of lumicitabine-40 mg/kg as LD (Dose 1) followed by 9 MD doses of lumicitabine 20 mg/kg twice a day. | ||
Reporting group title |
Lumicitabine 60/40 mg/kg LD/MD
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Reporting group description |
Subjects received a single dose of lumicitabine-60 mg/kg as LD (Dose 1) followed by 9 MD doses of lumicitabine 40 mg/kg twice a day. |
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End point title |
Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load [1] | ||||||||||||||||
End point description |
AUC of RSV viral load was measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assay of the mid-turbinate nasal swab.
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End point type |
Primary
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End point timeframe |
Day 1 (Post-dose; 0.25 and 2 hours) to Day 7 (Post-dose; 0.25 and 2 hours)
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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Notes [2] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [3] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [4] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. |
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No statistical analyses for this end point |
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End point title |
Number of Subjects with Emergent Adverse Event | ||||||||||||
End point description |
An AE is any untoward medical occurrence in a clinical study subject administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. 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. Safety analysis set was defined as all subjects who received at least 1 dose of study drug, analyzed as treated.
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End point type |
Secondary
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End point timeframe |
Approximately up to 28 days
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No statistical analyses for this end point |
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End point title |
Number of Subjects with Clinically Significant Physical Examinations Abnormalities | ||||||||||||
End point description |
The number of subjects with clinically significant physical examination (respiratory system, nose, ear, throat, facial and neck lymph nodes, and skin examination) abnormalities reported. Randomized or Treated set was defined as all subjects who were in the Randomized Analysis Set (all randomized subjects with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or all subjects treated (AST) set.
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End point type |
Secondary
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End point timeframe |
Approximately up to 28 days
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No statistical analyses for this end point |
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End point title |
Number of Subjects with Clinical Relevant Vital Signs Abnormalities | ||||||||||||||||||||||||||||||||||||
End point description |
The number of subjects with vital signs (temperature, pulse rate, respiratory rate, diastolic blood pressure, systolic blood pressure, oxygen saturation) abnormalities reported. Safety analysis set was defined as all subjects who received at least 1 dose of study drug, analyzed as treated.
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End point type |
Secondary
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End point timeframe |
Approximately up to 28 days
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No statistical analyses for this end point |
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End point title |
Number of Subjects with Electrocardiogram (ECG) Abnormalities | ||||||||||||||||||||||||
End point description |
The number of subjects with ECG (PR, QT, QRS, QTc intervals, and heart rate) abnormalities reported. Randomized or Treated set was defined as all subjects who were in the Randomized Analysis Set (all randomized subjects with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set.
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End point type |
Secondary
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End point timeframe |
Approximately up to 28 days
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No statistical analyses for this end point |
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End point title |
Number of Subjects with Laboratory Abnormalities (Worst Emergent DMID Toxicity Grades) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The number of subjects with Laboratory (hematology, serum chemistry, and urinalysis) abnormalities reported. Safety analysis set was defined as all subjects who received at least 1 dose of study drug, analyzed as treated.
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End point type |
Secondary
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End point timeframe |
Approximately up to 28 days
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No statistical analyses for this end point |
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End point title |
Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 (Metabolite of Lumicitabine) [5] | ||||||||||||||||||
End point description |
The Cmax is the maximum observed plasma concentration. Intent to Treat (ITT) set was defined as all randomized subjects who receive at least 1 dose of study. Here, "99999" indicates that the data was not estimable as only one subject was analyzed in the specified arm.
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End point type |
Secondary
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End point timeframe |
Day 1 and Day 5
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Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be reported for the specified arms only. |
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No statistical analyses for this end point |
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End point title |
AUC of JNJ-63549109 (Metabolite of Lumicitabine) [6] | ||||||||||||||||||
End point description |
AUC is the area under the plasma concentration-time curve. ITT set was defined as all randomized subjects who receive at least 1 dose of study. Here, "99999" indicates that the data was not estimable as only one subject was analyzed in the specified arm.
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End point type |
Secondary
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End point timeframe |
Day 1 and Day 5
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Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be reported for the specified arms only. |
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No statistical analyses for this end point |
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End point title |
Trough Observed Analyte Concentration (C[trough]) of JNJ-63549109 (Metabolite of Lumicitabine) [7] | ||||||||||||||||||
End point description |
C(trough) is trough observed analyte concentration of JNJ-63549109. ITT set was defined as all randomized subjects who receive at least 1 dose of study Here, "99999" indicates that the data was not estimable as only one subject was analyzed in the specified arm.
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End point type |
Secondary
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End point timeframe |
Day 1 and Day 5
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Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Endpoint was planned to be reported for the specified arms only. |
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No statistical analyses for this end point |
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End point title |
Predicted Concentration of JNJ-63549109 (Metabolite of Lumicitabine) at 12 hours Postdose (C12h) | ||||||||||||||||
End point description |
C12h is the predicted concentration of JNJ-63549109 at 12 hours Postdose. C12h is a model-based prediction. It was determined using a population pharmacokinetic (PK) model and based on the individual model predicted concentration-time profiles.
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End point type |
Secondary
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End point timeframe |
12 hours postdose
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Notes [8] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [9] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [10] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. |
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No statistical analyses for this end point |
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End point title |
Length of Hospital Stay | ||||||||||||||||||||||||||||||||||||||||||||
End point description |
Length of hospital stay is defined as the time from hospitalization to actual hospital discharge. Randomized or Treated (RT) set was defined as all subjects who were in the Randomized Analysis Set (all randomized subjects with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the all subjects treated (AST) set. Here ‘99999’ indicates that the subject was not analyzed for the respective arm.
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End point type |
Secondary
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End point timeframe |
Up to 28 days
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No statistical analyses for this end point |
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End point title |
Number of Subjects Admitted to the Intensive Care Unit (ICU) | ||||||||||||
End point description |
Number of subjects who were admitted to the ICU was reported. Randomized or Treated set was defined as all subjects who were in the Randomized Analysis Set (all randomized subjects with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set.
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End point type |
Secondary
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End point timeframe |
Up to 28 days
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No statistical analyses for this end point |
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End point title |
Duration of ICU Stay | ||||||||||||||||
End point description |
In the event that a subject required ICU, the duration for how long the subject remained in the ICU was reported. Randomized or Treated set was defined as all subjects who were in the Randomized Analysis Set (all randomized subjects with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set.
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End point type |
Secondary
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End point timeframe |
Up to 28 days
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No statistical analyses for this end point |
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End point title |
Number of Subjects who Required Supplemental Oxygen | ||||||||||||
End point description |
The number of subjects who required supplemental oxygen above pre-RSV infection status was reported. Randomized or Treated set was defined as all subjects who were in the Randomized Analysis Set (all randomized subjects with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set.
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End point type |
Secondary
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End point timeframe |
Up to 28 days
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No statistical analyses for this end point |
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End point title |
Number of Subjects who Required Non-invasive Mechanical Ventilation Support | ||||||||||||
End point description |
The number of subjects who required non-invasive mechanical ventilation support (that is, continuous positive airway pressure) above pre-RSV infection status was reported. Randomized or Treated set was defined as all subjects who were in the Randomized Analysis Set (all randomized subjects with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set.
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End point type |
Secondary
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End point timeframe |
Up to 28 days
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No statistical analyses for this end point |
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End point title |
Number of Subjects who Required Invasive Mechanical Ventilation Support | ||||||||||||
End point description |
The number of subjects who required invasive mechanical ventilation support (for example, endotracheal-mechanical ventilation or mechanical ventilation via tracheostomy) above pre-RSV infection status was reported. Randomized or Treated set was defined as all subjects who were in the Randomized Analysis Set (all randomized subjects with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set.
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End point type |
Secondary
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End point timeframe |
Up to 28 days
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No statistical analyses for this end point |
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End point title |
Duration of Supplemental Oxygen | ||||||||||||||||||||||||
End point description |
Duration of supplemental oxygen above pre-RSV infection status was assessed. Randomized or Treated set was defined as all subjects who were in the Randomized Analysis Set (all randomized subjects with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set. Here ‘99999’ indicates that the subject was not analyzed for the respective arm.
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End point type |
Secondary
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End point timeframe |
Up to 28 days
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No statistical analyses for this end point |
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End point title |
Duration of Non-invasive Mechanical Ventilation Support | ||||||||||||||||
End point description |
Duration of non-invasive mechanical ventilation support (that is, continuous positive airway pressure) to deliver oxygen above pre-RSV infection status was measured. Randomized or Treated set was defined as all subjects who were in the Randomized Analysis Set (all randomized subjects with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to 28 days
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Duration of Invasive Mechanical Ventilation Support | ||||||||||||||||
End point description |
Duration of invasive mechanical ventilation support (for example, endotracheal-mechanical ventilation or mechanical ventilation via tracheostomy) to deliver oxygen above pre-RSV infection status was measured. Randomized or Treated set was defined as all subjects who were in the Randomized Analysis Set (all randomized subjects with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to 28 days
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Time to no Longer Requiring Supplemental Oxygen | ||||||||||||||||||||||||
End point description |
Time to no longer requiring supplemental oxygen above pre-RSV infection status was reported. Randomized or Treated set was defined as all subjects who were in the Randomized Analysis Set (all randomized subjects with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set. Here ‘99999’ indicates that the subject was not analyzed for respective arm.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Up to 28 days
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||
End point title |
Time to Clinical Stability | ||||||||||||||||||||||||||||||||||||||||||||
End point description |
Time to clinical stability was defined as the time at which the following criteria are all met: normalization of blood oxygen level (return to baseline, by pulse oximetry) without the requirement of supplemental oxygen beyond baseline level, normalization of oral feeding, normalization of respiratory rate, and normalization of heart rate. Randomized or Treated set was defined as all subjects who were in the Randomized Analysis Set (all randomized subjects with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set. Here ‘99999’ indicates that the subject was not analyzed for respective arm.
|
||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Up to 28 days
|
||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Time From Initiation of Study Treatment Until Peripheral Capillary Oxygen Saturation (SpO2) Greater Than or Equal to (>=)93 Percent (%) on Room Air Among Subjects who were not on Supplemental Oxygen Prior to Onset of Respiratory Symptoms | ||||||||||||||||
End point description |
Time from initiation of study treatment until SpO2 >=93% on room air among subjects who were not on supplemental oxygen prior to the onset of respiratory symptoms was reported.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to 28 days
|
||||||||||||||||
|
|||||||||||||||||
Notes [11] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [12] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [13] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||
End point title |
Time for Respiratory Rate to Return to Pre-RSV Infection Status | ||||||||||||||||||||||||||||||||||||||||||||
End point description |
Time for the respiratory rate to return to pre-RSV infection status was measured. Randomized or Treated set was defined as all subjects who were in the Randomized Analysis Set (all randomized subjects with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set. Here ‘99999’ indicates that the subject was not analyzed for respective arm.
|
||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Up to 28 days
|
||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||
End point title |
Time for SpO2 to Return to Pre-RSV Infection Status | ||||||||||||||||||||||||||||||||||||||||||||
End point description |
Time for SpO2 to return to pre-RSV infection status was measured. Randomized or Treated set was defined as all subjects who were in the Randomized Analysis Set (all randomized subjects with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set. Here ‘99999’ indicates that the subject was not analyzed for respective arm.
|
||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Up to 28 days
|
||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||
End point title |
Time for Body Temperature to Return To Pre-RSV Infection Status | ||||||||||||||||||||||||||||||||||||||||||||
End point description |
Time for body temperature to return to pre-RSV infection status was measured. Randomized or Treated set was defined as all subjects who were in the Randomized Analysis Set (all randomized subjects with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set. Here ‘99999’ indicates that the subject was not analyzed for respective arm.
|
||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Up to 28 days
|
||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Number of Subjects With Acute Otitis Media | ||||||||||||
End point description |
Number of subjects with acute otitis media was reported. Randomized or Treated set was defined as all subjects who were in the Randomized Analysis Set (all randomized subjects with a randomization date at or before the date of the first intake of medication, or with a randomization date and a missing date for first medication intake, analyzed as randomized) and/or the AST set.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 28 days
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Duration of Signs and Symptoms of RSV Infection | ||||||||||||||||
End point description |
Duration of signs and symptoms of RSV infection was assessed.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to 28 days
|
||||||||||||||||
|
|||||||||||||||||
Notes [14] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [15] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [16] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Severity of Signs and Symptoms of RSV Infection Assessed by the Pediatric RSV Electronic Severity and Outcome Rating System (PRESORS) | ||||||||||||||||
End point description |
The severity of signs and symptoms of RSV infection were assessed by the PRESORS. PRESORS questions were answered by means of the following response scale: a lot less than usual, a little less than usual, about as much as usual, a little more than usual, a lot more than usual.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to 28 Days
|
||||||||||||||||
|
|||||||||||||||||
Notes [17] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [18] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [19] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
RSV Viral Load Over Time | ||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
RSV viral load over time was measured by qRT-PCR in the mid-turbinate nasal swab specimens. Intention-To-Treat-infected (ITT-i) set was defined as all randomly assigned subjects who receive at least 1 dose of study drug and who have an RSV infection confirmed by a polymerase chain reaction (PCR)-based assay at baseline or within 1 hour after the first study medication intake at the central laboratory.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Up to 28 days
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Peak Viral Load | ||||||||||||||||
End point description |
Peak viral load was measured by qRT-PCR in the mid-turbinate nasal swab specimens.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to 28 days
|
||||||||||||||||
|
|||||||||||||||||
Notes [20] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [21] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [22] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Time To Peak Viral Load | ||||||||||||||||
End point description |
Time to peak viral load was reported.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to 28 days
|
||||||||||||||||
|
|||||||||||||||||
Notes [23] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [24] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [25] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of Subjects with Decline of Viral Load | ||||||||||||||||
End point description |
Percentage of subjects with decline in viral load during treatment as measured by qRT-PCR was reported. ITT-i set was defined as all randomly assigned subjects who receive at least 1 dose of study drug and who have an RSV infection confirmed by a polymerase chain reaction (PCR)-based assay at baseline or within 1 hour after the first study medication intake at the central laboratory.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to 28 days
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Time to RSV Ribonucleic Acid (RNA) Being Undetectable | ||||||||||||||||
End point description |
Time to RSV RNA being undetectable (the time from initiation of study treatment until the time at which it is observed that the virus is undetectable in an assessment and after which time no virus positive assessment follows) was assessed as measured by qRT-PCR.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to 28 days
|
||||||||||||||||
|
|||||||||||||||||
Notes [26] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [27] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [28] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of Subjects with Undetectable RSV Viral Load | ||||||||||||||||
End point description |
Percentage of subjects with the undetectable viral load was reported.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to 28 days
|
||||||||||||||||
|
|||||||||||||||||
Notes [29] - As the study was terminated due to less number of subjects the efficacy results could not be drawn. [30] - As the study was terminated due to less number of subjects the efficacy results could not be drawn. [31] - As the study was terminated due to less number of subjects the efficacy results could not be drawn. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC of RSV RNA Viral Load From Baseline up to Day 10 | ||||||||||||||||
End point description |
AUC of RSV RNA viral load was measured in mid-turbinate nasal swabs and in the endotracheal sample.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline up to Day 10
|
||||||||||||||||
|
|||||||||||||||||
Notes [32] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [33] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [34] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC of RSV RNA Viral Load From Baseline up to Day 14 | ||||||||||||||||
End point description |
AUC of RSV RNA viral load was measured in midturbinate nasal swabs and in endotracheal samples.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline up to Day 14
|
||||||||||||||||
|
|||||||||||||||||
Notes [35] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [36] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [37] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
AUC of RSV Viral Load From Baseline Until 1 day (+2 Days) After the Last Dose of Study Drug | ||||||||||||||||
End point description |
AUC of RSV viral load was measured in midturbinate nasal swabs and in endotracheal samples.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline Until 1 day (+2 Days) After the Last Dose of Study Drug (approximately up to 10 days)
|
||||||||||||||||
|
|||||||||||||||||
Notes [38] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [39] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [40] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Number of Subjects With Postbaseline Changes in the RSV Polymerase L-gene and Other Regions of the RSV Genome Compared With Baseline Sequences | ||||||||||||||||
End point description |
Number of subjects were assessed for changes in the RSV polymerase L-gene (only if no mutations are seen in the L-gene) and other regions of the RSV genome compared with baseline sequences.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline up to 28 days
|
||||||||||||||||
|
|||||||||||||||||
Notes [41] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [42] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [43] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Acceptability of the Lumicitabine Formulation as Assessed by Parent(s)/Caregiver(s) electronic clinical outcome assessment (eCOA) | ||||||||||||||||
End point description |
Acceptability of the lumicitabine formulation was assessed by parent(s)/caregiver(s) eCOA.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to Day 6
|
||||||||||||||||
|
|||||||||||||||||
Notes [44] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [45] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [46] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Palatability of the Lumicitabine Formulation as Assessed by Parent(s)/Caregiver(s) eCOA | ||||||||||||||||
End point description |
Palatability (taste and texture) of the lumicitabine formulation was assessed by parent(s)/caregiver(s) eCOA.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to Day 6
|
||||||||||||||||
|
|||||||||||||||||
Notes [47] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [48] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. [49] - As study was terminated, due to less number of subjects result for this endpoint could not be drawn. |
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to 28 days
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Safety analysis set was defined as all subjects who received at least 1 dose of study drug, analyzed as treated.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received a single dose of lumicitabine-40 milligrams/kilogram (mg/kg) matched placebo as a loading dose (LD) (Dose 1) followed by 9 maintenance dose (MD) of lumicitabine-20 mg/kg matched placebo twice a day or a single dose of lumicitabine-60 mg/kg matched placebo LD (Dose 1) followed by nine lumicitabine-40 mg/kg matched placebo MD (Dose 2 to 10). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lumicitabine 60/40 mg/kg LD/MD
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received a single dose of lumicitabine-60 mg/kg as LD (Dose 1) followed by 9 MD doses of lumicitabine 40 mg/kg twice a day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lumicitabine 40/20 mg/kg LD/MD
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received a single dose of lumicitabine-40 mg/kg as LD (Dose 1) followed by 9 MD doses of lumicitabine 20 mg/kg twice a day. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
17 Aug 2017 |
This amendment was to remove furosemide, ibuprofen, and trimethoprim/sulfamethoxazole from the list of prohibited moderate/strong inhibitors of organic anion transporter 3. In addition, no food intake information with regard to study drug administration was collected for discharged subjects due to the minimal impact of food intake on trough levels (PK sample at Day 7). Furthermore, it was clarified that leftover samples from nasal swabs and PK testing only (not safety testing) could be used for exploratory biomarker analysis. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
Only 7 subjects were treated before the study was prematurely terminated. Due to this small number of treated subjects, statistical analysis was not conducted as planned. Hence it was not possible to evaluate the primary or secondary objectives. |