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

NCT ID: NCT03333317

Last Updated: 2019-12-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-24
• Study Completion Date: 2018-03-23

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.

Conditions

Respiratory Syncytial Viruses

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Regimen A (Low-Dose Lumicitabine)

Participants will receive a single 40 milligram per kilogram (mg/kg) loading dose (LD) (Dose 1) followed by nine 20 mg/kg maintenance doses (MDs) (Doses 2 to 10) of lumicitabine twice daily up to Day 5/6.

Group Type: EXPERIMENTAL

Lumicitabine

Intervention Type: DRUG

Participants will receive oral administration of lumicitabine.

Regimen B (High-Dose Lumicitabine)

Participants will receive a single 60 mg/kg LD (Dose 1) followed by nine 40 mg/kg MDs (Doses 2 to 10) of lumicitabine twice daily up to Day 5/6.

Group Type: EXPERIMENTAL

Lumicitabine

Intervention Type: DRUG

Participants will receive oral administration of lumicitabine.

Regimen C (Placebo)

Participants will receive either a single 40 mg/kg placebo LD (Dose 1) followed by nine 20 mg/kg maintenance dose (MDs) (Doses 2 to 10) of placebo twice daily or single 60 mg/kg placebo LD (Dose 1) followed by nine 40 mg/kg placebo MDs (Doses 2 to 10), twice daily up to Day 5/6.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive oral administration of matching placebo.

Interventions

Lumicitabine

Participants will receive oral administration of lumicitabine.

Intervention Type: DRUG

Placebo

Participants will receive oral administration of matching placebo.

Intervention Type: DRUG

Other Intervention Names

ALS-008176; JNJ-64041575

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)

• Minimum Eligible Age: 28 Days
• Maximum Eligible Age: 36 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

MemorialCare Research Miller Children's and Women's Hospital Long Beach

Long Beach, California, United States

The Children's Mercy Hospital

Kansas City, Missouri, United States

SUNY Upstate Medical University

Syracuse, New York, United States

Jacobi Medical Center

The Bronx, New York, United States

West Virginia University

Morgantown, West Virginia, United States

American Family Children's Hospital

Madison, Wisconsin, United States

Huderf

Brussels, , Belgium

McMaster Children's Hospital

Hamilton, Ontario, Canada

Heim Pal Gyermekkorhaz, Borgyogyaszati Osztaly

Budapest, , Hungary

Velkey László Gyermekegészségügyi Központ

Miskolc, , Hungary

Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz

Nyíregyháza, , Hungary

National Hospital Organization Fukuoka Hospital

Fukuoka, , Japan

Fukuoka Children's Hospital

Fukuoka, , Japan

National Hospital Organization Fukuyama Medical Center

Fukuyama, , Japan

Fukuyama City Hospital

Fukuyama, , Japan

JA Hiroshima General Hospital

Hatsukaichi, , Japan

Hirosaki National Hospital

Hirosaki, , Japan

National Hospital Organization Kanazawa Medical Center

Kanazawa, , Japan

National Hospital Organization Kokura Medical Center

Kitakyushu, , Japan

National Hospital Organization Niigata National Hospital

Niigata, , Japan

Nakano Children's Hospital

Osaka, , Japan

Takatsuki General Hospital

Osaka, , Japan

NHO Beppu Medical Center

Ōita, , Japan

Ota Memorial Hospital

Ōta-ku, , Japan

NHO Saitama National Hospital

Saitama, , Japan

Gunma Children's Medical Center

Shibukawa, , Japan

Shikoku Medical Center for Children and Adults

Zentsujichó, , Japan

Plejady Medical Center

Malopolska, , Poland

Specialistic Hospital Center for Mother and Child

Poznan, , Poland

Countries

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

References

Oey A, McClure M, Symons JA, Chanda S, Fry J, Smith PF, Luciani K, Fayon M, Chokephaibulkit K, Uppala R, Bernatoniene J, Furuno K, Stanley T, Huntjens D, Witek J; 503 and RSV2004 Study Groups. Lumicitabine, an orally administered nucleoside analog, in infants hospitalized with respiratory syncytial virus (RSV) infection: Safety, efficacy, and pharmacokinetic results. PLoS One. 2023 Jul 19;18(7):e0288271. doi: 10.1371/journal.pone.0288271. eCollection 2023.

Reference Type: DERIVED

PMID: 37467213 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-001862-56

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

64041575RSV2004

Identifier Type: OTHER

Identifier Source: secondary_id

CR108367

Identifier Type: -

Identifier Source: org_study_id