Evidence map›Paper›PMID 39278975›Full record

ArticleInfectious diseases and therapy2024

A Pooled Analysis of Eight Clinical Studies Suggests a Link Between Influenza-Like Symptoms and Pharmacodynamics of the Toll-Like Receptor-7 Agonist Vesatolimod.

Sharon A Riddler, Constance A Benson, Cynthia Brinson, Steven G Deeks, Edwin DeJesus, Anthony Mills, Michael F Para, Moti N Ramgopal, Yanhui Cai, Yanan Zheng and 9 more

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Article in Infectious diseases and therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

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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

19 authors.

Sharon A RiddlerDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Constance A BensonDepartment of Medicine, UC San Diego, San Diego, CA, USA.
Cynthia BrinsonCentral Texas Clinical Research, Austin, TX, USA.
Steven G DeeksDepartment of Medicine, University of California San Francisco, San Francisco, CA, USA.
Edwin DeJesusOrlando Immunology Center, Orlando, FL, USA.
Anthony MillsMen's Health Foundation, Los Angeles, CA, USA.
Michael F ParaThe Ohio State University Wexner Medical Center, Columbus, OH, USA.
Moti N RamgopalMidway Specialty Care Center, Fort Pierce, FL, USA.
Yanhui CaiGilead Sciences, Inc., Foster City, CA, USA.
Yanan ZhengGilead Sciences, Inc., Foster City, CA, USA.
Liao ZhangGilead Sciences, Inc., Foster City, CA, USA.
Wendy JiangGilead Sciences, Inc., Foster City, CA, USA.
Xiaopeng LiuGilead Sciences, Inc., Foster City, CA, USA.
Donovan VerrillGilead Sciences, Inc., Foster City, CA, USA.
Daina LimGilead Sciences, Inc., Foster City, CA, USA.
Christiaan R de VriesGilead Sciences, Inc., Foster City, CA, USA.
Jeffrey J WallinGilead Sciences, Inc., Foster City, CA, USA.
Elena VendrameGilead Sciences, Inc., Foster City, CA, USA.
Devi SenGuptaGilead Sciences, Inc., Foster City, CA, USA. devi.sengupta@gilead.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionVesatolimod is a Toll-like receptor-7 (TLR7) agonist in clinical development as part of a combination regimen for human immunodeficiency virus (HIV) cure. Influenza-like symptoms associated with TLR7-mediated immune activation have been reported in clinical trials of vesatolimod. Therefore, a broader understanding of the safety profile of vesatolimod and association with dose and mechanism of action will help inform future clinical studies.

methodsIn this analysis, data on flu-like adverse events of interest (AEIs) were pooled from eight clinical studies in which 606 participants either received single or multiple doses of vesatolimod (0.3-12 mg; n = 505) or placebo (n = 101). Vesatolimod pharmacokinetics, inflammatory responses, and pharmacodynamics were assessed.

resultsThe incidence of flu-like AEIs was higher with vesatolimod versus placebo (19% [96/505] vs. 8% [8/101]) and increased with vesatolimod dose and exposure. Most flu-like AEIs with vesatolimod were grade 1 or 2 severity (55% [53 of 96] grade 1; 35% [34 of 96] grade 2) with onset primarily after the first and second dose. Occurrence of flu-like AEIs after doses 1-3 was predictive of reoccurrence after later doses. Dose-dependent elevations of pharmacodynamic biomarkers (interferon-stimulated gene 15, 2'-5'-oligoadenylate synthetase 1, myxovirus resistance-1, interferon-α, interleukin-1 receptor antagonist, interferon-γ-induced protein 10, interferon-inducible T-cell-α chemoattractant) observed in participants with flu-like AEIs suggest a link with vesatolimod mechanism of action.

conclusionsFlu-like AEIs associated with vesatolimod administration were typically mild but increased with exposure, which may be predicted by the response to initial doses. The data suggest that adaptive clinical monitoring could help maximize pharmacodynamic responses and balance adverse events in future clinical trials of vesatolimod.

Indexed as

Influenza-like adverse eventsSafetyToll-like receptor-7 agonistVesatolimod

Identifiers

PMID39278975
PMCPMC11499514

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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 OpenQuestion graph.