A 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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03333317
• Date of registration: 16/10/2017
• Prospective Registration: Yes
• Primary sponsor: Janssen Research & Development, LLC
• Public title: A 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
• Scientific title: 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
• Date of first enrolment: November 24, 2017
• Target sample size: 7
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03333317
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, Chile, Colombia, Czechia, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Malaysia, Netherlands, New Zealand, Panama, Poland, Portugal, Slovakia, Spain, Sweden, Taiwan, Thailand, Ukraine, United Kingdom, United States

Contacts

• Name: Janssen Research & Development, LLC Clinical Trial
• Affiliation: Janssen Research & Development, LLC

Key inclusion & exclusion criteria

Inclusion Criteria:

- Participants hospitalized (or in emergency room [ER]) at the time of randomization and
unlikely to be discharged for the first 24 hours after randomization

- Participants diagnosed with respiratory syncytial virus (RSV) infection using a
polymerase chain reaction (PCR)-based molecular diagnostic assay, with or without
co-infection with another respiratory pathogen (respiratory virus or bacteria)

- Participants who have an acute respiratory illness with signs and symptoms consistent
with a viral infection (for example, fever, cough, nasal congestion, runny nose, sore
throat, myalgia, lethargy, shortness of breath, or wheezing) with onset less than or
equal to <=5 days from the anticipated time of randomization. Onset of symptoms is
defined as the first time (within 1 hour) the parent(s)/caregiver(s) becomes aware of
respiratory or systemic symptoms of RSV infection

- With the exception of the symptoms related to the RSV infection or defined comorbid
condition for severe RSV disease (prematurity at birth [participant's gestational age
was less than {<}37 weeks; for infants <1 year old at randomization], bronchopulmonary
dysplasia, congenital heart disease, other congenital diseases, Down syndrome,
neuromuscular impairment, or cystic fibrosis), participant must be medically stable on
the basis of physical examination, medical history, vital signs/peripheral capillary
oxygen saturation (SpO2), and electrocardiogram (ECG) performed at screening. If there
are abnormalities, they must be consistent with the underlying condition in the study
population and/or the RSV infection. This determination must be recorded in the
participant's source documents and initialed by the investigator. Participants with
comorbidities will be allowed to be enrolled once the Independent Data Monitoring
Committee (IDMC) has reviewed the pharmacokinetic (PK) and safety data of the highest
dose that will be used in this study and once the IDMC has recommended opening
recruitment to this group. Sites will be notified when the restriction is lifted

- The participant's estimated glomerular filtration rate (eGFR) is not below the lower
limit of normal for the participant's age

Exclusion Criteria:

- Participants who are not expected to survive for more than 48 hours

- Participants who have had major thoracic or abdominal surgery in the 6 weeks prior to
randomization

- Participants who have a known or suspected immunodeficiency (except immunoglobulin A
[IgA] deficiency), such as a known human immunodeficiency virus infection

- Participants being treated with extracorporeal membrane oxygenation

- Participant receiving chronic oxygen therapy at home prior to admission

- Participants who have a poorly functioning gastrointestinal tract (that is, unable to
absorb drugs or nutrition via enteral route)



Age minimum: N/A
Age maximum: 36 Months
Gender: All

Health Condition(s) or Problem(s) studied

Respiratory Syncytial Viruses

Intervention(s)

Drug: Placebo

Drug: Lumicitabine

Primary Outcome(s)

Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load [Time Frame: Day 1 to 7: Predose, 0.25 and 2 hours postdose]

Secondary Outcome(s)

Area Under Plasma Concentration-time Curve (AUC) of JNJ-63549109 (Metabolite of Lumicitabine) [Time Frame: Day 1 and Day 5]

Number of Participants Admitted to the Intensive Care Unit (ICU) [Time Frame: Up to 28 days]

Number of Participants Who Required Non-invasive Mechanical Ventilation Support [Time Frame: Up to 28 days]

Percentage of Participants With Decline of Viral Load [Time Frame: Up to 28 days]

Percentage of Participants With Undetectable RSV Viral Load [Time Frame: Up to 28 days]

Duration of ICU Stay [Time Frame: Up to 28 days]

Number of Participants With Emergent Adverse Event [Time Frame: Up to 28 days]

Predicted Concentration of JNJ-63549109 (Metabolite of Lumicitabine) at 12 Hours Postdose (C12h) [Time Frame: 12 hours postdose]

AUC of RSV Viral Load From Baseline Until 1 Day After the Last Dose of Study Drug [Time Frame: Baseline Until 1 Day after the last dose of study drug (up to 10 days)]

Time for Respiratory Rate to Return to Pre-RSV Infection Status [Time Frame: Up to 28 days]

Time to no Longer Requiring Supplemental Oxygen [Time Frame: Up to 28 days]

Number of Participants With Electrocardiogram (ECG) Abnormalities [Time Frame: Up to 28 days]

Time to RSV Ribonucleic Acid (RNA) Being Undetectable [Time Frame: Up to 28 days]

Duration of Signs and Symptoms of RSV Infection [Time Frame: Up to 28 days]

Duration of Supplemental Oxygen [Time Frame: Up to 28 days]

Severity of Signs and Symptoms of RSV Infection Assessed by the Pediatric RSV Electronic Severity and Outcome Rating System (PRESORS) [Time Frame: Up to 28 days]

Time From Initiation of Study Treatment Until Peripheral Capillary Oxygen Saturation (SpO2) Greater Than or Equal to (>=)93 Percent (%) on Room Air Among Participants Who Were Not on Supplemental Oxygen Prior to Onset of Respiratory Symptoms [Time Frame: Up to 28 days]

Time to Clinical Stability [Time Frame: Up to 28 days]

Trough Observed Analyte Concentration (C[Trough]) of JNJ-63549109 (Metabolite of Lumicitabine) [Time Frame: Day 1 and Day 5]

Acceptability and Palatability of Lumicitabine Formulation as Assessed by Clinician Electronic Clinical Outcome Assessment (eCOA) [Time Frame: Up to Day 6]

Duration of Non-invasive Mechanical Ventilation Support [Time Frame: Up to 28 days]

Length of Hospital Stay [Time Frame: Up to 28 days]

AUC of RSV RNA Viral Load From Baseline up to Day 14 [Time Frame: Baseline up to Day 14]

Duration of Invasive Mechanical Ventilation Support [Time Frame: Up to 28 days]

Number of Participants With Acute Otitis Media [Time Frame: Up to 28 days]

Number of Participants With Emergent Postbaseline Changes in the RSV Polymerase L-gene and Other Regions of the RSV Genome Compared With Baseline Sequences [Time Frame: Baseline up to 28 days]

Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades) [Time Frame: Up to 28 days]

Number of Participants Who Required Supplemental Oxygen [Time Frame: Up to 28 days]

Number of Participants With Clinically Significant Physical Examinations Abnormalities [Time Frame: Up to 28 days]

Peak Viral Load [Time Frame: Up to 28 days]

RSV Viral Load Over Time [Time Frame: On Day 2, 3, 4, 5, 6, 7, 10, 14 and 28]

Time To Peak Viral Load [Time Frame: Up to 28 days]

AUC of RSV RNA Viral Load From Baseline up to Day 10 [Time Frame: Baseline up to Day 10]

Number of Participants Who Required Invasive Mechanical Ventilation Support [Time Frame: Up to 28 days]

Time for Body Temperature to Return To Pre-RSV Infection Status [Time Frame: Up to 28 days]

Time for SpO2 to Return to Pre-RSV Infection Status [Time Frame: Up to 28 days]

Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 (Metabolite of Lumicitabine) [Time Frame: Day 1 and Day 5]

Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities [Time Frame: Up to 28 days]

Secondary ID(s)

64041575RSV2004

2017-001862-56

CR108367

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 05/12/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03333317