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

NCT03333317 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: CR1083672017-001862-5664041575RSV2004
• Study Type: interventional
• Target: 7
• Locations: 6 countries
• Sites: 29

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).

Conditions

Respiratory Syncytial Viruses

Outcome Measures

Primary Outcomes (1)

• Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load

  AUC of RSV viral load was measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assay of the mid-turbinate nasal swab.

  Day 1 to 7: Predose, 0.25 and 2 hours postdose

Secondary Outcomes (38)

• Number of Participants With Emergent Adverse Event

  Up to 28 days

• Number of Participants With Clinically Significant Physical Examinations Abnormalities

  Up to 28 days

• Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities

  Up to 28 days

• Number of Participants With Electrocardiogram (ECG) Abnormalities

  Up to 28 days

• Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades)

  Up to 28 days

Study Arms (3)

Regimen A (Low-Dose Lumicitabine)

EXPERIMENTAL

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.

Drug: Lumicitabine

Regimen B (High-Dose Lumicitabine)

EXPERIMENTAL

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.

Drug: Lumicitabine

Regimen C (Placebo)

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Lumicitabine DRUG

Participants will receive oral administration of lumicitabine.

Also known as: ALS-008176, JNJ-64041575

Regimen A (Low-Dose Lumicitabine); Regimen B (High-Dose Lumicitabine)

Placebo DRUG

Participants will receive oral administration of matching placebo.

Regimen C (Placebo)

Eligibility Criteria

• Age: 28 Days - 36 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (29)

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

Long Beach, California, 90806, United States

Location

The Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

American Family Children's Hospital

Madison, Wisconsin, 53792, United States

Location

Huderf

Brussels, 1020, Belgium

Location

McMaster Children's Hospital

Hamilton, Ontario, L85 4K1, Canada

Location

Heim Pal Gyermekkorhaz, Borgyogyaszati Osztaly

Budapest, 1089, Hungary

Location

Velkey László Gyermekegészségügyi Központ

Miskolc, 3501, Hungary

Location

Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz

Nyíregyháza, 4400, Hungary

Location

National Hospital Organization Fukuoka Hospital

Fukuoka, 811-1394, Japan

Location

Fukuoka Children's Hospital

Fukuoka, 813-0017, Japan

Location

National Hospital Organization Fukuyama Medical Center

Fukuyama, 720-8520, Japan

Location

Fukuyama City Hospital

Fukuyama, 721-8511, Japan

Location

JA Hiroshima General Hospital

Hatsukaichi, 738-8503, Japan

Location

Hirosaki National Hospital

Hirosaki, 036-8545, Japan

Location

National Hospital Organization Kanazawa Medical Center

Kanazawa, 920-8650, Japan

Location

National Hospital Organization Kokura Medical Center

Kitakyushu, 802-8533, Japan

Location

National Hospital Organization Niigata National Hospital

Niigata, 945-8585, Japan

Location

Nakano Children's Hospital

Osaka, 535-0022, Japan

Location

Takatsuki General Hospital

Osaka, 569-1192, Japan

Location

NHO Beppu Medical Center

Ōita, 874-0011, Japan

Location

Ota Memorial Hospital

Ōta-ku, 373-8585, Japan

Location

NHO Saitama National Hospital

Saitama, 351-0102, Japan

Location

Gunma Children's Medical Center

Shibukawa, 377-8577, Japan

Location

Shikoku Medical Center for Children and Adults

Zentsujichó, 765-8507, Japan

Location

Plejady Medical Center

Malopolska, 30-349, Poland

Location

Specialistic Hospital Center for Mother and Child

Poznan, 60-595, Poland

Location

Related Publications (1)

• 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.

  PMID: 37467213 DERIVED

MeSH Terms

Interventions

4'-chloromethyl-2'-deoxy-3',5'-di-O-isobutyryl-2'-fluorocytidine

Limitations and Caveats

Only 7 participants 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.

Results Point of Contact

• Title: Medical Leader
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2017
• First Posted: November 6, 2017
• Study Start: November 24, 2017
• Primary Completion: March 23, 2018
• Study Completion: March 23, 2018
• Last Updated: December 23, 2019
• Results First Posted: December 5, 2019

Record last verified: 2019-12

Locations

BE (1); JP (16); US (6); PL (2); CA (1); HU (3)