Evidence mapPaperPMID 30566758Full record

Trial reportBritish journal of clinical pharmacology2019

Target engagement and cellular fate of otelixizumab: a repeat dose escalation study of an anti-CD3ε mAb in new-onset type 1 diabetes mellitus patients.

Georgios Vlasakakis, Antonella Napolitano, Ruth Barnard, Kim Brown, Jonathan Bullman, David Inman, Bart Keymeulen, David Lanham, Quentin Leirens, Alexander MacDonald and 6 more

Open access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph

Trial report in British journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.5field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 12 citations in OpenAlex.

  1. Trial
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  6. Therapeutic Antibodies in Medicine.Molecules (Basel, Switzerland) · 2023
    Review
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  8. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 4 countries.

Georgios VlasakakisResearch and Development, GlaxoSmithKline, London, UK.ORCID 0000-0002-7390-9712
Antonella NapolitanoResearch and Development, GlaxoSmithKline, London, UK.
Ruth BarnardResearch and Development, GlaxoSmithKline, London, UK.
Kim BrownProject Management, GlaxoSmithKline, London, UK.
Jonathan BullmanResearch and Development, GlaxoSmithKline, London, UK.
David InmanResearch and Development, GlaxoSmithKline, London, UK.
Bart KeymeulenAcademic Hospital and Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
David LanhamEurofins Pharma Bioanalysis Services UK Ltd.
Quentin LeirensSGS Exprimo NV, Generaal de Wittelaan 19A b5, B-2800, Mechelen, Belgium.
Alexander MacDonaldOncology Quantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, Astrazeneca, Cambridge, UK.
Enrica MezzalanaSGS Exprimo NV, Generaal de Wittelaan 19A b5, B-2800, Mechelen, Belgium.
Kevin PageResearch and Development, GlaxoSmithKline, London, UK.
Minesh PatelEurofins Pharma Bioanalysis Services UK Ltd.
Caroline O SavageResearch and Development, GlaxoSmithKline, London, UK.
Stefano ZamunerResearch and Development, GlaxoSmithKline, London, UK.
Andre van MaurikResearch and Development, GlaxoSmithKline, London, UK.
GlaxoSmithKline (United Kingdom) · GBDeloitte (United States) · USEurofins (United Kingdom) · GBAstraZeneca (United Kingdom) · GBVrije Universiteit Brussel · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsThis paper describes the pharmacological findings from a study where otelixizumab, an anti-CD3ɛ mAb, was dosed in new onset Type 1 diabetes mellitus (NOT1DM) patients. This is the first time that the full dose-response of an anti-CD3ɛ mAb has been investigated in the clinic. The data have been validated using a previously developed pharmacokinetic/pharmacodynamic (PK/PD) model of otelixizumab to simulate the interplay between drug administration, CD3ɛ target engagement and downmodulation.

methodsPatients were randomized to control or active treatment with otelixizumab (1:4), administered via infusion over 6 days, in a dose-ascending study consisted of three cohorts (n = 10 per cohort) at doses of 9, 18 or 27 mg respectively. The study allowed quantification of otelixizumab PK, CD3ɛ target engagement and its pharmacodynamic effect (CD3ε/TCR modulation on circulating T lymphocytes).

resultsOtelixizumab concentrations increased and averaged to 364.09 (54.3), 1625.55 (72.5) and 2781.35 (28.0) ng ml

conclusionsData from this study revealed maximum target engagement and CD3ɛ/TCR modulation is achieved at doses of 18, 27 mg of otelixizumab. These findings can be useful in guiding dose selection in clinical trials with anti-CD3ɛ mAbs.

Indexed as

AdolescentAdultAntibodies, Monoclonal, HumanizedCD3 ComplexDiabetes Mellitus, Type 1Dose-Response Relationship, DrugFemaleHumansInfusions, IntravenousMaleMolecular Targeted TherapyReceptors, Antigen, T-CellT-LymphocytesTreatment OutcomeYoung AdultAntibodies, Monoclonal, HumanizedCD3 ComplexCD3E protein, humanotelixizumabReceptors, Antigen, T-Celldose-responseimmunoinflammationOtelixizumabPK/PDtarget engagementtype 1 diabetes

Identifiers

PMID30566758
PMCPMC6422670
OpenAlexW2904749369

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.