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Record W4313647319 · doi:10.1186/s41231-022-00134-4

RLS-0071, a dual-targeting anti-inflammatory peptide - biomarker findings from a first in human clinical trial

2023· article· en· W4313647319 on OpenAlexaff
Jessica Goss, Pamela S. Hair, Parvathi S. Kumar, Giuseppina Iacono, Laura Redden, Gaetano Morelli, Neel K. Krishna, Ulrich Thienel, Kenji M. Cunnion

Bibliographic record

VenueTranslational Medicine Communications · 2023
Typearticle
Languageen
FieldImmunology and Microbiology
TopicNeutrophil, Myeloperoxidase and Oxidative Mechanisms
Canadian institutionsAltasciences (Canada)
Fundersnot available
KeywordsMyeloperoxidasePeptideBiomarkerPharmacokineticsMedicinePharmacologyInternal medicineInflammationChemistryBiochemistry

Abstract

fetched live from OpenAlex

Abstract Background RLS-0071 is a novel 15 amino acid peptide dual-targeting anti-inflammatory inhibitor of complement and neutrophil effectors. RLS-0071 inhibits classical complement pathway activation at C1 and blocks the enzymatic activity of myeloperoxidase that leads to the generation of hypochlorous acid and induces NETosis. This peptide is being developed for the treatment of neonatal hypoxic ischemic encephalopathy (HIE) and neutrophilic pulmonary diseases. Methods This was a first in human clinical trial in healthy volunteers to assess safety and pharmacokinetics of single and multiple ascending doses of RLS-0071. Results RLS-0071 single and multiple doses were not associated with any clinically significant changes in safety parameters, laboratory test results or ECG measurements. Adverse events were similar between active drug and placebo groups. The pharmacokinetic profile demonstrated dose proportionality and two-compartment kinetics with rapid tissue distribution. Exploratory biomarker and target engagement assays demonstrated dose dependent classical complement pathway inhibition and myeloperoxidase binding. Discussion/Conclusion RLS-0071 was shown to be safe and well-tolerated at all doses tested with rapid tissue distribution and target engagement for both the classical complement pathway and myeloperoxidase. The findings are supportive of further clinical development and evaluation of RLS-0071 in conditions such as HIE and acute pulmonary diseases. Trial registration ClinicalTrials.gov Identifier: NCT05298787 March 28, 2022. Retrospectively registered.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.011
Threshold uncertainty score0.036

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0110.002

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.122
GPT teacher head0.373
Teacher spread0.251 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations6
Published2023
Admission routes1
Has abstractyes

Explore more

Same venueTranslational Medicine CommunicationsSame topicNeutrophil, Myeloperoxidase and Oxidative MechanismsFrench-language works237,207