A Study to Assess the Pharmacokinetics, Safety, and Tolerability of Multiple Doses of Orally Administered JNJ-53718678 in Infants Hospitalized With Respiratory Syncytial Virus (RSV) Infection

NCT02593851 | Terminated Phase 1 FDA Drug

• 3 other identifiers: CR1079452015-002003-2853718678RSV1005
• Study Type: interventional
• Target: 45
• Locations: 10 countries
• Sites: 39

Brief Summary

The purpose of this study is to evaluate pharmacokinetics, safety, tolerability, antiviral activity, and impact on the clinical course of Respiratory Syncytial Virus (RSV) infection after multiple oral doses of JNJ-53718678 at different doses and/or dosing regimens in infants (greater than \[\>\] 1 month to less than or equal to \[\<=\] 24 months of age) who are hospitalized with RSV infection.

Conditions

Respiratory Syncytial Virus Infections; Virus Diseases

Keywords

Respiratory Syncytial Virus Infections; JNJ-53718678; Placebo; Infants

Outcome Measures

Primary Outcomes (6)

• Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678

  The Cmax is the maximum observed plasma concentration.

  Days 1, 2 and 3

• Trough Plasma Concentration (Ctrough) of JNJ-53718678

  The Ctrough is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen.

  Days 1, 2 and 3

• Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)

  The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval.

  Days 1, 2 and 3

• Total Apparent Clearance (CL/F) of JNJ-53718678

  Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  Days 1, 2 and 3

• Apparent Volume of Distribution (Vd/F) of JNJ-53718678

  Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vd/F) is influenced by the fraction absorbed.

  Days 1, 2 and 3

• Number of Participants With Adverse Events

  An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

  Up to Follow-up (Day 28)

Secondary Outcomes (14)

• Area Under the Viral Load-time Curve (VL AUC)

  Up to Follow-up (Day 28)

• Amount of Viral Load Over Time

  Up to Follow-up (Day 28)

• Number of viral particles at Peak Viral Load

  Up to Follow-up (Day 28)

• Time To Peak Viral Load

  Up to Follow-up (Day 28)

• Number of Participants Reaching Undetectability of virus Between First Administration of Study Drug and Day 28

  Day 1 to Day 28

Study Arms (16)

Part 1: Cohort 1a

EXPERIMENTAL

Participants (greater than or equal to \[\>=\] 6 months and less than or equal to \[\<=\] 24 months of age) will receive JNJ-53718678, 2 milligram per kilogram body weight (mg/kg) oral solution once daily on Day 1 to Day 7. Dose and/or dosing regimen may be adapted in subsequent cohorts based on the review of the safety/tolerability and full pharmacokinetic data from Cohort 1a.

Drug: JNJ-53718678

Part 1: Cohort 1b

EXPERIMENTAL

Participants (\>= 6 months and \<= 24 months of age) will receive total daily dose of 6 mg/kg JNJ-53718678 oral solution or placebo \[either in once daily \[qd\] or twice daily \[bid\]) on Day 1 to Day 7.

Drug: JNJ-53718678; Drug: Placebo

Part 1: Cohort 1c

EXPERIMENTAL

Participants (\>= 6 months and \<= 24 months of age) will receive total daily dose of 18 mg/kg JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7.

Drug: JNJ-53718678; Drug: Placebo

Part 1: Cohort 1d

EXPERIMENTAL

Participants (\>= 6 months and \<= 24 months of age) will receive JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7. The cohort 1d is optional and may be included at the discretion of the sponsor.

Drug: JNJ-53718678; Drug: Placebo

Part 1: Cohort 1e

EXPERIMENTAL

Participants (\>= 6 months and \<= 24 months of age) will receive JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7. The cohort 1e is optional and may be included at the discretion of the sponsor.

Drug: JNJ-53718678; Drug: Placebo

Part 1: Cohort 2a

EXPERIMENTAL

Participants (\>= 3 months and less than \[\<\] 6 months of age) will receive total daily dose of 1.5 mg/kg JNJ-53718678 oral solution \[either in a qd or a bid regimen\] on Day 1 to Day 7.

Drug: JNJ-53718678

Part 1: Cohort 2b

EXPERIMENTAL

Participants (\>=3 months and \< 6 months of age) will receive total daily dose of 4.5 mg/kg JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7.

Drug: JNJ-53718678; Drug: Placebo

Part 1: Cohort 2c

EXPERIMENTAL

Participants (\>= 3 months and \< 6 months of age) will receive total daily dose of 13.5 mg/kg JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7

Drug: JNJ-53718678; Drug: Placebo

Part 1: Cohort 2d

EXPERIMENTAL

Participants (\>= 3 months and \< 6 months of age) will receive JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7. The cohort 2d is optional and may be included at the discretion of the sponsor.

Drug: JNJ-53718678; Drug: Placebo

Part 1: Cohort 2e

EXPERIMENTAL

Participants (\>= 3 months and \< 6 months of age) will receive JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7. The cohort 2e is optional and may be included at the discretion of the sponsor.

Drug: JNJ-53718678; Drug: Placebo

Part 1: Cohort 3a

EXPERIMENTAL

Participants (greater than (\>) 1 month and \< 3 months of age) will receive total daily dose of 1 mg/kg JNJ-53718678 oral solution \[either in a qd or a bid regimen\] on Day 1 to Day 7.

Drug: JNJ-53718678

Part 1: Cohort 3b

EXPERIMENTAL

Participants (\> 1 month and \< 3 months of age) will receive total daily dose of 3 mg/kg JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7.

Drug: JNJ-53718678; Drug: Placebo

Part 1: Cohort 3c

EXPERIMENTAL

Participants (\> 1 month and \< 3 months of age) will receive total daily dose of 9 mg/kg JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7.

Drug: JNJ-53718678; Drug: Placebo

Part 1: Cohort 3d

EXPERIMENTAL

Participants (\> 1 month and \< 3 months of age) will receive JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7. The cohort 3d is optional and may be included at the discretion of the sponsor.

Drug: JNJ-53718678; Drug: Placebo

Part 1: Cohort 3e

EXPERIMENTAL

Participants (\> 1 month and \< 3 months of age) will receive JNJ-53718678 oral solution or placebo \[either in a qd or a bid regimen\] on Day 1 to Day 7. The cohort 3e is optional and may be included at the discretion of the sponsor.

Drug: JNJ-53718678; Drug: Placebo

Part 2: Cohort f

EXPERIMENTAL

Participants of all age groups will receive daily dose of JNJ-53718678 oral solution or placebo, either in a qd or a bid regimen on Days 1 to 7.

Drug: JNJ-53718678; Drug: Placebo

Interventions

JNJ-53718678 DRUG

JNJ-53718678 oral solution will be administered once or twice daily for 7 days.

Part 1: Cohort 1a; Part 1: Cohort 1b; Part 1: Cohort 1c; Part 1: Cohort 1d; Part 1: Cohort 1e; Part 1: Cohort 2a; Part 1: Cohort 2b; Part 1: Cohort 2c; Part 1: Cohort 2d; Part 1: Cohort 2e; Part 1: Cohort 3a; Part 1: Cohort 3b; Part 1: Cohort 3c; Part 1: Cohort 3d; Part 1: Cohort 3e; Part 2: Cohort f

Placebo DRUG

Placebo oral solution will be administered once or twice daily for 7 days.

Part 1: Cohort 1b; Part 1: Cohort 1c; Part 1: Cohort 1d; Part 1: Cohort 1e; Part 1: Cohort 2b; Part 1: Cohort 2c; Part 1: Cohort 2d; Part 1: Cohort 2e; Part 1: Cohort 3b; Part 1: Cohort 3c; Part 1: Cohort 3d; Part 1: Cohort 3e; Part 2: Cohort f

Eligibility Criteria

• Age: 1 Month - 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participant has presented at the hospital for suspected Respiratory Syncytial Virus (RSV) infection within 72 hours prior to Screening completion
• Participant has been hospitalized for this suspected RSV infection
• Participant has been diagnosed with RSV infection using a polymerase chain reaction (PCR)-based assay, preferably commercially available locally
• Participant was born after a normal term pregnancy (greater than or equal to 37 weeks and 0 days)
• A legally acceptable representative of the participant must sign an Informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study, are willing for their child to participate in the study, are willing for their child to remain in the hospital for the first 3 days of dosing (even if not clinically indicated), and are willing/able to adhere to the prohibitions and restrictions specified in the protocol and study procedures

You may not qualify if:

• Participant who had major surgery within the 28 days prior to randomization or planned major surgery through the course of the study
• Participant has major congenital anomalies or known cytogenetic disorders
• Participant has known or suspected immunodeficiency, such as known human immunodeficiency virus (HIV) infection
• Participant has known or suspected hepatitis B or C infection
• Participant is upon current admission initially hospitalized in the Intensive care unit (ICU) and/or in need of invasive endotracheal mechanical ventilation

Sponsors & Collaborators

• Janssen Sciences Ireland UC: lead

Study Sites (39)

Unknown Facility

Kirksville, Missouri, United States

Location

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Bahía Blanca, Argentina

Location

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City of Buenos Aires, Argentina

Location

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Córdoba, Argentina

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Geelong, Australia

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Hobart, Australia

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Westmead, Australia

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Anderlecht, Belgium

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Brussels, Belgium

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Charleroi, Belgium

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Edegem, Belgium

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Leuven, Belgium

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Lier, Belgium

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Curitiba, Brazil

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Porto Alegre, Brazil

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Ribeirão Preto, Brazil

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Rio de Janeiro, Brazil

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São Paulo, Brazil

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Freiburg im Breisgau, Germany

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Hamm, Germany

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Heidelberg, Germany

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München, Germany

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Hoofddorp, Netherlands

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Utrecht, Netherlands

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Cebu City, Philippines

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Manila, Philippines

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Almería, Spain

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Barcelona, Spain

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Esplugues de Llobregat, Spain

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Getafe, Spain

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Madrid, Spain

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Málaga, Spain

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Santiago de Compostela, Spain

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Seville, Spain

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Valencia, Spain

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Gothenburg, Sweden

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Linköping, Sweden

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Lund, Sweden

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Malmo, Sweden

Location

Related Publications (1)

• Martinon-Torres F, Rusch S, Huntjens D, Remmerie B, Vingerhoets J, McFadyen K, Ferrero F, Baraldi E, Rojo P, Epalza C, Stevens M. Pharmacokinetics, Safety, and Antiviral Effects of Multiple Doses of the Respiratory Syncytial Virus (RSV) Fusion Protein Inhibitor, JNJ-53718678, in Infants Hospitalized With RSV Infection: A Randomized Phase 1b Study. Clin Infect Dis. 2020 Dec 17;71(10):e594-e603. doi: 10.1093/cid/ciaa283.

  PMID: 32201897 DERIVED

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections; Virus Diseases

Interventions

JNJ-53718678

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Infections

Study Officials

• Janssen Sciences Ireland UC Clinical Trial

  Janssen Sciences Ireland UC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2015
• First Posted: November 2, 2015
• Study Start: December 4, 2015
• Primary Completion: March 21, 2017
• Study Completion: November 10, 2017
• Last Updated: December 6, 2019

Record last verified: 2019-12

Locations

ES (9); SE (4); AU (3); BE (6); AR (3); NL (2); US (1); BR (5); DE (4); PH (2)