PMID- 32201897
OWN - NLM
STAT- MEDLINE
DCOM- 20210428
LR  - 20210428
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Print)
IS  - 1058-4838 (Linking)
VI  - 71
IP  - 10
DP  - 2020 Dec 17
TI  - 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.
PG  - e594-e603
LID - 10.1093/cid/ciaa283 [doi]
AB  - BACKGROUND: This phase 1b study evaluated the pharmacokinetics, safety, and 
      antiviral effects of the respiratory syncytial virus (RSV)-specific fusion 
      inhibitor JNJ-53718678 (JNJ-8678) in hospitalized RSV-infected patients aged > 1 
      to </=24 months. METHODS: Patients categorized by age (cohort 1: >/=6 to </=24 months; 
      cohort 2: >/=3 to < 6 months; cohort 3: > 1 to < 3 months) were randomized to oral 
      JNJ-8678 or placebo once daily for 7 days. Dose increases followed data review 
      committee recommendations (cohort 1: 2/6/8/9 mg/kg; cohort 2: 1.5/4.5/6 mg/kg; 
      cohort 3: 1/3/5 mg/kg). Cohort 1 included a 9 mg/kg dose, as target exposures 
      were not reached at lower doses. Sparse pharmacokinetic samples were assessed 
      using population pharmacokinetics modeling. Safety was assessed by adverse events 
      (AEs), laboratory tests, and electrocardiograms. To assess antiviral effects, RSV 
      RNA viral load from nasal swabs was quantified over time using 
      reverse-transcription quantitative polymerase chain reaction. RESULTS: Patients 
      received JNJ-8678 (n = 37) or placebo (n = 7). Pharmacokinetic parameters were 
      similar at the highest doses for cohorts 1-3 (area under the plasma 
      concentration-time curve from time of administration up to 24 hours postdosing at 
      day 7: 35 840, 34 980, and 39 627 ng x hour/mL, respectively). Two grade 3 AEs 
      were reported (both bronchiolitis; 1 JNJ-8678, 1 placebo), reported as serious 
      AEs; all other AEs were grade 1 or 2. Two additional serious AEs were reported 
      (rhinitis [JNJ-8678]; pneumonia [placebo]). No deaths, grade 4 AEs, or AEs 
      leading to discontinuation were reported. Median RSV viral load change from 
      baseline in JNJ-8678 vs placebo by day 3 was -1.98 vs -0.32 log10 copies/mL. 
      CONCLUSIONS: In RSV-infected infants, JNJ-8678 was well tolerated. Target 
      exposures were reached and antiviral activity was observed. CLINICAL TRIALS 
      REGISTRATION: NCT02593851.
CI  - (c) The Author(s) 2020. Published by Oxford University Press for the Infectious 
      Diseases Society of America.
FAU - Martinon-Torres, Federico
AU  - Martinon-Torres F
AD  - Translational Pediatrics and Infectious Diseases, Pediatrics Department, Hospital 
      Clinico Universitario de Santiago de Compostela, University of Santiago, La 
      Coruna, Spain.
FAU - Rusch, Sarah
AU  - Rusch S
AD  - Quantitative Sciences, Janssen Research and Development, Beerse, Belgium.
FAU - Huntjens, Dymphy
AU  - Huntjens D
AD  - Quantitative Sciences, Janssen Research and Development, Beerse, Belgium.
FAU - Remmerie, Bart
AU  - Remmerie B
AD  - Quantitative Sciences, Janssen Research and Development, Beerse, Belgium.
FAU - Vingerhoets, Johan
AU  - Vingerhoets J
AD  - Clinical Virology, Janssen Research and Development, Beerse, Belgium.
FAU - McFadyen, Katie
AU  - McFadyen K
AD  - Global Clinical Development Operations Infectious Diseases, Janssen Research and 
      Development, Washington, District of Columbia, USA.
FAU - Ferrero, Fernando
AU  - Ferrero F
AD  - Hospital General de Ninos "Pedro de Elizalde," Buenos Aires, Argentina.
FAU - Baraldi, Eugenio
AU  - Baraldi E
AD  - Women's and Children's Health Department, University Hospital of Padova, Padova, 
      Italy.
FAU - Rojo, Pablo
AU  - Rojo P
AD  - Pediatric Infectious Disease Unit, Hospital Universitario 12 de Octubre, 
      Universidad Complutense, Instituto de Investigacion Hospital 12 de Octubre, 
      Translational Research Network in Pediatric Infectology, Madrid, Spain.
FAU - Epalza, Cristina
AU  - Epalza C
AD  - Pediatric Infectious Disease Unit, Hospital Universitario 12 de Octubre, 
      Universidad Complutense, Instituto de Investigacion Hospital 12 de Octubre, 
      Translational Research Network in Pediatric Infectology, Madrid, Spain.
FAU - Stevens, Marita
AU  - Stevens M
AD  - Global Clinical Development Infectious Diseases, Janssen Research and 
      Development, Beerse, Belgium.
LA  - eng
SI  - ClinicalTrials.gov/NCT02593851
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Antiviral Agents)
RN  - 0 (Imidazolidines)
RN  - 0 (Indoles)
RN  - 0 (JNJ-53718678)
SB  - IM
MH  - Aged
MH  - Antiviral Agents/therapeutic use
MH  - Double-Blind Method
MH  - Humans
MH  - *Imidazolidines/therapeutic use
MH  - Indoles/therapeutic use
MH  - Infant
MH  - *Respiratory Syncytial Virus Infections/drug therapy
PMC - PMC7744997
OTO - NOTNLM
OT  - JNJ-53718678
OT  - JNJ-8678
OT  - fusion inhibitor
OT  - infants
OT  - respiratory syncytial virus
EDAT- 2020/03/24 06:00
MHDA- 2021/04/29 06:00
PMCR- 2020/03/23
CRDT- 2020/03/24 06:00
PHST- 2019/09/12 00:00 [received]
PHST- 2020/03/20 00:00 [accepted]
PHST- 2020/03/24 06:00 [pubmed]
PHST- 2021/04/29 06:00 [medline]
PHST- 2020/03/24 06:00 [entrez]
PHST- 2020/03/23 00:00 [pmc-release]
AID - 5810953 [pii]
AID - ciaa283 [pii]
AID - 10.1093/cid/ciaa283 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2020 Dec 17;71(10):e594-e603. doi: 10.1093/cid/ciaa283.