Evidence map›Paper›PMID 40967767›Full record

Trial reportThe European respiratory journal2025

Two randomised controlled phase 2 studies of the oral neutrophil elastase inhibitor alvelestat in alpha-1 antitrypsin deficiency.

J Michael Wells, Ingrid L Titlestad, Hanan Tanash, Alice M Turner, Kenneth R Chapman, Umur Ş Hatipoğlu, Monica P Goldklang, Jeanine M D'Armiento, Cheryl S Pirozzi, M Bradley Drummond and 16 more

Abstract readRandomized Controlled TrialClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The European respiratory journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors.

J Michael WellsDivision of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA jmwells@uabmc.edu.ORCID https://orcid.org/0000-0001-9612-5454
Ingrid L TitlestadDepartment of Respiratory Medicine, Odense University Hospital, Odense, Denmark.
Hanan TanashDepartment of Respiratory Medicine, Skåne University Hospital, Malmö, Sweden.
Alice M TurnerSchool of Health Sciences, University of Birmingham, Birmingham, UK.ORCID https://orcid.org/0000-0002-5947-3254
Kenneth R ChapmanDepartment of Medicine, University of Toronto, Toronto, ON, Canada.ORCID https://orcid.org/0000-0002-2498-9859
Umur Ş HatipoğluDepartment of Pulmonary Medicine, Cleveland Clinic, Cleveland, OH, USA.
Monica P GoldklangDepartment of Anesthesiology, Columbia University, New York, NY, USA.
Jeanine M D'ArmientoDepartment of Anesthesiology, Columbia University, New York, NY, USA.
Cheryl S PirozziDivision of Respiratory, Critical Care, and Occupational Pulmonary Medicine, University of Utah, Salt Lake City, UT, USA.
M Bradley DrummondDepartment of Medicine, Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina, Chapel Hill, NC, USA.
Igor Z BarjaktarevicDepartment of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Wissam M ChatilaDepartment of Thoracic Medicine and Surgery, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
Megan S DevineUT Health Science Center Tyler, Tyler, TX, USA.
Charlie StrangeDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, SC, USA.
Robert A SandhausDepartment of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health, Denver, CO, USA.
Jacqueline M ParkinMereo BioPharma Group plc, London, UK.
Elizabeth WestfallDivision of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Vivian Y LinDivision of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Robin ParksSchool of Public Health, Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
Hui-Chien KuoSchool of Public Health, Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
Adzoa EkueMereo BioPharma Group plc, London, UK.
Kelly L MoffittProAxsis Ltd, Belfast, UK.
Jamie InshawExploristics Ltd, Belfast, UK.
Inmaculada AbanSchool of Public Health, Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
Mark T DransfieldDivision of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Robert A StockleyUniversity of Birmingham Research Laboratories, Queen Elizabeth Hospital Birmingham, Birmingham, UK.

Funding

AZD9688: A First in Class Disease Modifying Therapy to Treat Alpha-1 Antitrypsin Deficiency a Genetically Linked Orphan DiseaseUH3TR002450 · NCATS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ABAN, INMACULADA, DRANSFIELD, MARK T · 2018 to 2021
$4.5M
Matrikines and COPD-PHR01HL148215 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI WELLS, JAMES MICHAEL · 2019 to 2023
$2.4M
AZD9688: A First in Class Disease Modifying Therapy to Treat Alpha-1 Antitrypsin Deficiency a Genetically Linked Orphan DiseaseUG3TR002450 · NCATS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CUTTER, GARY R, DRANSFIELD, MARK T · 2018 to 2018
$624k
NCATS NIH HHS UG3 TR002450NCATS NIH HHS UH3 TR002450NHLBI NIH HHS R01 HL148215
6 · The paper itself

Abstract

backgroundAlpha-1 antitrypsin deficiency (AATD) is a genetic disorder that causes emphysema from lack of the alpha-1 antitrypsin (AAT) serpin antiprotease, leading to protease-antiprotease imbalance. Weekly intravenous AAT therapy (augmentation) is the only specific treatment available. Alvelestat is an oral inhibitor of neutrophil elastase (NE) in development as a novel approach to AATD therapy. Here, we tested the safety and mechanistic efficacy of alvelestat in severe AATD.

methodsWe conducted two complementary, double-blind, randomised, placebo-controlled, 12-week trials, incorporating two doses of alvelestat in AATD. ATALANTa investigated 120 mg twice daily, including a subset of participants also receiving augmentation; ASTRAEUS tested 120 and 240 mg twice daily without augmentation. Primary and secondary end-points were the change in blood NE (the putative target) and its activity in AATD (Aα-Val

resultsWe enrolled 161 participants (63 in ATALANTa and 98 in ASTRAEUS). Blood NE was significantly suppressed in both studies at both doses, with the greatest effect (>90% suppression) at alvelestat 240 mg twice daily. There was no effect of alvelestat 120 mg on disease activity biomarkers, while 240 mg demonstrated significant reduction in Aα-Val

conclusionsAlvelestat effectively suppressed NE and its activity at both doses, but only the 240 mg twice-daily dose demonstrated relevant efficacy compared to placebo on disease activity biomarkers with a favourable safety profile. These findings support progression of the 240 mg twice-daily dose into a clinical end-point study.

Indexed as

alpha 1-Antitrypsin DeficiencyLeukocyte ElastaseAdministration, OralAdultAgedalpha 1-AntitrypsinDouble-Blind MethodFemaleHumansMaleMiddle AgedTreatment Outcomealpha 1-AntitrypsinLeukocyte Elastase

Identifiers

PMID40967767
PMCPMC12713387

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Registered trials

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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.