Cited by 366Monoclonal and Polyclonal Antibodies ResearchRespiratory viral infections researchBiosimilars and Bioanalytical Methods

A Novel Investigational Fc-Modified Humanized Monoclonal Antibody, Motavizumab-YTE, Has an Extended Half-Life in Healthy Adults

Open access
Robbie, Gabriel J., Criste, Ryan, Dall'Acqua, William F., Jensen, Kathryn, Patel, Nita K., Losonsky, Genevieve A., Griffin, M. Pamela·2013·Antimicrobial Agents and Chemotherapy

Abstract

The study objective was to evaluate the pharmacokinetics (PK), antidrug antibody (ADA), and safety of motavizumab-YTE (motavizumab with amino acid substitutions M252Y/S254T/T256E [YTE]), an Fc-modified anti-respiratory syncytial virus (RSV) monoclonal antibody. Healthy adults ( n = 31) were randomized to receive a single intravenous (i.v.) dose of motavizumab-YTE or motavizumab (0.3, 3, 15, or 30 mg/kg) and followed for 240 days. Clearance of motavizumab-YTE was significantly lower (71% to 86%) and the half-life ( t 1/2 ) was 2- to 4-fold longer than with motavizumab. However, similar peak concentrations and volume-of-distribution values, indicative of similar distribution properties, were seen at all dose levels. The sustained serum concentrations of motavizumab-YTE were fully functional, as shown by RSV neutralizing activity that persisted for 240 days with motavizumab-YTE versus 90 days postdose for motavizumab. Safety and incidence of ADA were comparable between groups. In this first study of an Fc-modified monoclonal antibody in humans, motavizumab-YTE was well tolerated and exhibited an extended half-life of up to 100 days. (This study has been registered at ClinicalTrials.gov under registration no. NCT00578682.)

Integrity signals

Registry

Crossref · 10.1128/aac.01285-13

Cites

17 of 17 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Improved understanding of the IgG-FcRn interaction along with advances in protein engineering has led to opportunities to engineer mAbs with extended half-life.

    “Improved understanding of the IgG‐FcRn interaction along with advances in protein engineering has led to opportunities to engineer mAbs with extended half‐life.32”
  • M252Y/S254T/T256E (YTE) mutations on motavizumab led to a 10-fold increase in affinity for human FcRn at pH 6.0 with no change in affinity at pH 7.4 and significantly increased its half-life in monkeys and in healthy adult humans.

    “M252Y/S254T/T256E (YTE) mutations on motavizumab led to a 10‐fold increase in affinity for human FcRn at pH 6.0 with no change in affinity at pH 7.4 and significantly increased its half‐life in monkeys and in healthy adult humans.32”

Cites

Flagged first, then by citations

1 of the 18 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Robbie, G. J., Criste, R., Dall'Acqua, W. F., Jensen, K., Patel, N. K., Losonsky, G. A., & Griffin, M. P.
Affiliations
  • Clinical Pharmacology and DMPK, MedImmune, Gaithersburg, Maryland, USA
  • Antibody Discovery and Protein Engineering, MedImmune, Gaithersburg, Maryland, USA
  • Biostatistics, MedImmune, Gaithersburg, Maryland, USA
  • Research and Development, Infectious Disease, MedImmune, Gaithersburg, Maryland, USA
  • Clinical Research and Development, MedImmune, Gaithersburg, Maryland, USA
Venue
Antimicrobial Agents and Chemotherapy
Published
2013-12
Volume
57
Issue
12
Pages
6147-6153
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
OpenAlex
W2148090354
Cited by
366
References
18
Citations by year
2026: 31 · 2025: 26 · 2024: 33 · 2023: 37 · 2022: 47 · 2021: 22 · 2020: 20 · 2019: 26 · 2018: 26 · 2017: 38 · 2016: 19 · 2015: 25 · 2014: 14 · 2013: 1
FWCI
15.26
Type
journal article
Language
en
Open access
Locations
  • Antimicrobial Agents and Chemotherapy (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
  • Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
Keywords
respiratory syncytial virus, pharmacokinetics, extended half-life, clearance, amino acid substitutions, antidrug antibodies, drug safety, healthy volunteers
MeSH terms
Adult, Antiviral Agents, Double-Blind Method, Female, Half-Life, Humans, Immunoglobulin Fc Fragments, Injections, Intravenous, Male, Metabolic Clearance Rate, Drugs, Investigational, Antibodies, Monoclonal, Humanized

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review