Clinical trial NCT03333317: 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
Official 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Respiratory Syncytial Viruses
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-11-06
Enrollment: 7
Sex: ALL
Minimum age (years): 28
Maximum age (years): 36
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine in hospitalized infants and children who are 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).

Detailed description: RSV is a leading cause of lower respiratory tract disease in infants. Most infants and children who get RSV recover fully after 1-2 weeks, but RSV infection can sometimes worsen and may lead to hospitalization and admission into an intensive care unit. The main purpose of this study is to learn how well the study drug (lumicitabine, also known as JNJ-64041575 or ALS-008176) works, how the human body handles the study drug, which dose of the study drug is effective for treatment of RSV infection in infants/children and how safe it is compared to a placebo (placebo looks just like lumicitabine \[given in same way\] but has no effect against RSV). Approximately up to 180 participants aged between 28 days to 36 months and hospitalized with RSV infection will take part in this world-wide study.

Eligibility 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)

Primary outcomes:
measure: Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load
timeFrame: Day 1 to 7: Predose, 0.25 and 2 hours postdose
Secondary outcomes:
measure: Number of Participants With Emergent Adverse Event
timeFrame: Up to 28 days
measure: Number of Participants With Clinically Significant Physical Examinations Abnormalities
timeFrame: Up to 28 days
measure: Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities
timeFrame: Up to 28 days
measure: Number of Participants With Electrocardiogram (ECG) Abnormalities
timeFrame: Up to 28 days
measure: Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades)
timeFrame: Up to 28 days
measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 (Metabolite of Lumicitabine)
timeFrame: Day 1 and Day 5
measure: Area Under Plasma Concentration-time Curve (AUC) of JNJ-63549109 (Metabolite of Lumicitabine)
timeFrame: Day 1 and Day 5
measure: Trough Observed Analyte Concentration (C[Trough]) of JNJ-63549109 (Metabolite of Lumicitabine)
timeFrame: Day 1 and Day 5
measure: Predicted Concentration of JNJ-63549109 (Metabolite of Lumicitabine) at 12 Hours Postdose (C12h)
timeFrame: 12 hours postdose
measure: Length of Hospital Stay
timeFrame: Up to 28 days
measure: Number of Participants Admitted to the Intensive Care Unit (ICU)
timeFrame: Up to 28 days
measure: Duration of ICU Stay
timeFrame: Up to 28 days
measure: Number of Participants Who Required Supplemental Oxygen
timeFrame: Up to 28 days
measure: Number of Participants Who Required Non-invasive Mechanical Ventilation Support
timeFrame: Up to 28 days
measure: Number of Participants Who Required Invasive Mechanical Ventilation Support
timeFrame: Up to 28 days
measure: Duration of Supplemental Oxygen
timeFrame: Up to 28 days
measure: Duration of Non-invasive Mechanical Ventilation Support
timeFrame: Up to 28 days
measure: Duration of Invasive Mechanical Ventilation Support
timeFrame: Up to 28 days
measure: Time to no Longer Requiring Supplemental Oxygen
timeFrame: Up to 28 days
measure: Time to Clinical Stability
timeFrame: Up to 28 days
measure: 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
timeFrame: Up to 28 days
measure: Time for Respiratory Rate to Return to Pre-RSV Infection Status
timeFrame: Up to 28 days
measure: Time for SpO2 to Return to Pre-RSV Infection Status
timeFrame: Up to 28 days
measure: Time for Body Temperature to Return To Pre-RSV Infection Status
timeFrame: Up to 28 days
measure: Number of Participants With Acute Otitis Media
timeFrame: Up to 28 days
measure: Duration of Signs and Symptoms of RSV Infection
timeFrame: Up to 28 days
measure: Severity of Signs and Symptoms of RSV Infection Assessed by the Pediatric RSV Electronic Severity and Outcome Rating System (PRESORS)
timeFrame: Up to 28 days
measure: RSV Viral Load Over Time
timeFrame: On Day 2, 3, 4, 5, 6, 7, 10, 14 and 28
measure: Peak Viral Load
timeFrame: Up to 28 days
measure: Time To Peak Viral Load
timeFrame: Up to 28 days
measure: Percentage of Participants With Decline of Viral Load
timeFrame: Up to 28 days
measure: Time to RSV Ribonucleic Acid (RNA) Being Undetectable
timeFrame: Up to 28 days
measure: Percentage of Participants With Undetectable RSV Viral Load
timeFrame: Up to 28 days
measure: AUC of RSV RNA Viral Load From Baseline up to Day 10
timeFrame: Baseline up to Day 10
measure: AUC of RSV RNA Viral Load From Baseline up to Day 14
timeFrame: Baseline up to Day 14
measure: AUC of RSV Viral Load From Baseline Until 1 Day After the Last Dose of Study Drug
timeFrame: Baseline Until 1 Day after the last dose of study drug (up to 10 days)
measure: Number of Participants With Emergent Postbaseline Changes in the RSV Polymerase L-gene and Other Regions of the RSV Genome Compared With Baseline Sequences
timeFrame: Baseline up to 28 days
measure: Acceptability and Palatability of Lumicitabine Formulation as Assessed by Clinician Electronic Clinical Outcome Assessment (eCOA)
timeFrame: Up to Day 6
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: MemorialCare Research Miller Children's and Women's Hospital Long Beach
state: California
city: Kansas City
country: United States
facility: The Children's Mercy Hospital
state: Missouri
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Madison
country: United States
facility: American Family Children's Hospital
state: Wisconsin
city: Bruxelles
country: Belgium
facility: Huderf
city: Hamilton
country: Canada
facility: McMaster Children's Hospital
state: Ontario
city: Budapest
country: Hungary
facility: Heim Pal Gyermekkorhaz, Borgyogyaszati Osztaly
city: Miskolc
country: Hungary
facility: Velkey László Gyermekegészségügyi Központ
city: Nyíregyháza
country: Hungary
facility: Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz
city: Fukuoka-shi
country: Japan
facility: National Hospital Organization Fukuoka Hospital
city: Fukuoka
country: Japan
facility: Fukuoka Children's Hospital
city: Fukuyama
country: Japan
facility: National Hospital Organization Fukuyama Medical Center
city: Fukuyama
country: Japan
facility: Fukuyama City Hospital
city: Hatsukaichi
country: Japan
facility: JA Hiroshima General Hospital
city: Hirosaki
country: Japan
facility: Hirosaki National Hospital
city: Kanazawa
country: Japan
facility: National Hospital Organization Kanazawa Medical Center
city: Kitakyushu
country: Japan
facility: National Hospital Organization Kokura Medical Center
city: Niigata
country: Japan
facility: National Hospital Organization Niigata National Hospital
city: Oita
country: Japan
facility: NHO Beppu Medical Center
city: Osaka
country: Japan
facility: Nakano Children's Hospital
city: Osaka
country: Japan
facility: Takatsuki General Hospital
city: Ota
country: Japan
facility: Ota Memorial Hospital
city: Saitama
country: Japan
facility: NHO Saitama National Hospital
city: Shibukawa
country: Japan
facility: Gunma Children's Medical Center
city: Zentsuji
country: Japan
facility: Shikoku Medical Center for Children and Adults
city: Malopolska
country: Poland
facility: Plejady Medical Center
city: Poznań
country: Poland
facility: Specialistic Hospital Center for Mother and Child
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: