1958. Antiviral Effects, Pharmacokinetics (PK) and Safety of the Respiratory Syncytial Virus (RSV) Fusion Protein Inhibitor, JNJ-53718678 (JNJ-8678), in RSV-infected Infants with Bronchiolitis, in the Phase 1b Study 53718678RSV1005
Session: Poster Abstract Session: Clinical Trials
Saturday, October 6, 2018
Room: S Poster Hall
Posters
  • 1111070 ID Week RSV Poster 2200x1100mm_eposter.pdf (1.9 MB)
  • Background: JNJ-8678 is a RSV-specific fusion inhibitor and a potential new treatment for respiratory infections caused by RSV. Data from a Phase 1b study of PK, safety and antiviral effects in hospitalised RSV-infected infants are presented.

    Methods: 37 and 7 patients, respectively, were randomised to JNJ-8678 (ascending doses, Table) or placebo (PBO) treatment once daily for 7 days. PK assessments were based on sparse sampling using a population PK model in adults scaled for pediatrics, accounting for allometric principles and maturation of drug clearance pathways. Safety was evaluated by AE reporting, lab and ECG assessments. Antiviral activity was assessed by measuring viral load (VL) using a quantitative RT-PCR assay for RSV RNA from nasal swabs.

    Results: Sparse PK data are described by an integrated PK model (Table) and indicated PK parameters for different dose levels were similar across age groups. Treatment with JNJ-8678 appeared to reduce VL more rapidly than PBO (Fig). Median change in VL from baseline (BL) in JNJ-8678-treated patients (combined dose groups) vs PBO was -1.98 vs -0.32 log10 copies/mL at Day 3. Mean differences in change from BL (90% CI) of JNJ-8678 (combined dose groups) vs PBO on Days 2 and 3 were estimated -1.33 (-2.26; -0.39) and -1.62 (-2.55; -0.69) log10 copies/mL, respectively (general linear model, adjusted for BL VL; p≤0.05). There was a clear separation between JNJ-8678 and PBO, but no evident exposure-response relationship. JNJ-8678 was generally well tolerated with no new safety signals compared to adults and no dose relationship with AEs or lab abnormalities were observed.

    Conclusion: This dataset in RSV-infected infants showed a clear trend for an early antiviral effect of JNJ-8678, which was similar across dose groups. JNJ-8678 treatment was generally well tolerated.

     

    Table PK data by dose/age group

     

    Dose

    Dose (mg/kg)
    All n=4

    Age (months)

    AUC24 Day 7

    Mean±SD

    Ctrough Day 7

    Mean±SD

    Low

    1

    1–3

    5121±471

    87±16

    1.5

    3–6

    6236±578

    83±18

    2

    6–24

    5631±605

    39±14

    Mid

    3

    1–3

    17867±1747

    345±64

    4.5

    3–6

    21965±2147

    346±73

    6

    6–24

    19693±2213

    170±60

    Intermediate

    8

    6–24

    27454±3108

    256±88

    High

    5

    1–3

    32478±3194

    675±120

    6

    3–6

    30722±3015

    510±105

    9

    6–24

    31445±3565

    303±103

     

    Federico Martinon-Torres, MD, PhD, Assoc Prof1, Sarah Rusch, MSc2, Dymphy Huntjens, PhD2, Bart Remmerie, Chem Eng2, Johan Vingerhoets, PhD3, Katie McFadyen, MPH4, Fernando Ferrero, Md, PhD5, Eugenio Baraldi, MD, FCCP6, Pablo Rojo Conejo, MD, PhD7, Cristina Epalza, MD7 and Marita Stevens, MD8, (1)Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain, (2)Janssen Research & Development, Beerse, Belgium, (3)Janssen Research & Development Infectious Diseases, Beerse, Belgium, (4)Global Clinical Development Operations Infectious Diseases, Janssen Research & Development, Raritan, NJ, (5)Hospital General de Niños "Pedro de Elizalde,", Buenos Aires, Argentina, (6)Women's and Children's Health Department, University of Padova, Padova, Italy, (7)Pediatric Infectious Disease Unit, Hospital Universitario 12 de Octubre, Universidad Complutense, Instituto de Investigación Hospital 12 de Octubre (imas12), RITIP, Madrid, Spain, (8)Global Clinical Development Infectious Diseases, Janssen Research & Development, Beerse, Belgium

    Disclosures:

    F. Martinon-Torres, Pfizer: Consultant , Consulting fee . SPMSD: Consultant , Consulting fee . GSK: Consultant , Consulting fee .

    S. Rusch, Janssen: Employee and Shareholder , Salary .

    D. Huntjens, Janssen: Employee and Shareholder , Salary .

    B. Remmerie, Janssen: Employee and Shareholder , Salary .

    J. Vingerhoets, Janssen: Employee and Shareholder , Salary .

    K. McFadyen, Janssen: Employee and Shareholder , Salary .

    F. Ferrero, None

    E. Baraldi, Abbvie: Lectures , Speaker honorarium . Chiesi Farmaceutici: Consultant , Consulting fee . Novartis: Consultant , Consulting fee . Janssen: Consultant , Consulting fee .

    P. Rojo Conejo, None

    C. Epalza, None

    M. Stevens, Janssen: Employee and Shareholder , Salary .

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