A 12-week Study Treating Participants Who Have alpha1-antitrypsin-related COPD With Alvelestat (MPH966) or Placebo.
ASTRAEUS
A Phase 2, Proof-of-concept, Multicentre, Double-blind, Randomised, Dose-ascending, Sequential Group, Placebo-controlled Study to Evaluate the Mechanistic Effect, Safety, and Tolerability of 12 Weeks Twice Daily Oral Administration of Alvelestat (MPH966) in Participants With Alpha-1 Antitrypsin Deficiency.
2 other identifiers
interventional
99
8 countries
26
Brief Summary
The purpose of this study is to investigate the effect of alvelestat (an oral neutrophil elastase inhibitor) on blood and sputum biomarkers in patients with PiZZ, null or rare variant phenotype/genotype alpha-1 anti-trypsin deficient lung disease. Change in a number of different blood and sputum biomarkers related to lung damage, inflammation and elastase activity will be measured over a 12 week period. The effect on lung function and respiratory symptoms will also be measured.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Oct 2018
Typical duration for phase_2
26 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 20, 2018
CompletedFirst Posted
Study publicly available on registry
August 17, 2018
CompletedStudy Start
First participant enrolled
October 29, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 2, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
March 30, 2022
CompletedApril 14, 2022
April 1, 2022
3.3 years
June 20, 2018
April 6, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change from baseline on blood biomarkers of neutrophil elastase activity compared to baseline and placebo
Within-individual change from baseline up to end of treatment in: * Blood neutrophil elastase activity * Blood Aα-Val 360 levels * Plasma desmosine/isodesmosine levels
12 weeks
Secondary Outcomes (1)
Change from baseline on other blood biomarkers of neutrophil elastase activity
12 weeks
Other Outcomes (2)
Change from baseline in St. George's Respiratory Questionnaire (SGRQ-C) to end of treatment
12 weeks
Change from baseline in pulmonary function
12 weeks
Study Arms (3)
Placebo oral tablet
PLACEBO COMPARATORAlvelestat oral tablet - dose 1
ACTIVE COMPARATORMPH966
Alvelestat oral tablet - dose 2
ACTIVE COMPARATORMPH966
Interventions
twice daily administration
twice daily administration
Eligibility Criteria
You may qualify if:
- Patients with a confirmed diagnosis of alpha-1-anti-trypsin deficiency and a PiZZ, null or other rare geno/phenotype and serum anti-alpha1 antitrypsin levels of less than 11uM
- FEV1 ≥20% predicted
- Computerised tomography (CT) scan evidence of emphysema
- Non-smokers
You may not qualify if:
- Primary diagnosis of bronchiectasis
- An ongoing acute exacerbation of the underlying lung disease
- Underlying liver disease or abnormal liver function tests
- Previous augmentation therapy within 6 months of dosing
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mereo BioPharmalead
- Syneos Healthcollaborator
Study Sites (26)
University of Alabama, Birmingham (UAB)
Birmingham, Alabama, 35294, United States
UCLA Medical Center
Los Angeles, California, 90095, United States
UC Davis Medical Centre
Sacramento, California, 95817, United States
PMG Research of Wilmington
Wilmington, North Carolina, 28401, United States
UZ Gent
Ghent, 9000, Belgium
UZ Leuven
Leuven, 3000, Belgium
The University Lung Clinic
Edmonton, Alberta, T6G 2C8, Canada
Centre for Heart Lung Innovation, St Pauls Hospital
Vancouver, British Columbia, V6Z 1Y6, Canada
Inspiration Research Ltd
Toronto, Ontario, M5T 3A9, Canada
University of Saskatchewan Royal University Hospital
Saskatoon, Saskatchewan, S7N 0W8, Canada
Aarhus Universitetshospital
Aarhus, 8200, Denmark
Gentofte Hospital
Hellerup, 2900, Denmark
Synddansk Universitet (SDU) - Odense University
Odense, 5000, Denmark
Instytut Gruzilicy Chorob Pluc
Warsaw, 01-138, Poland
Hospital Univ Clinico San Carlos
Madrid, Spain
Hospital Sierrallana
Torrelavega, Spain
CTC Gothia Forum Sahlgrenska University Hospital
Gothenburg, 41345, Sweden
Lund University Hospital
Lund, 22185, Sweden
University Hospitals Birmingham NHS Foundation Trust
Birmingham, B15 2GW, United Kingdom
Cambridge University Hospitals Foundation NHS Trust
Cambridge, CB2 0QQ, United Kingdom
University Hospital Coventry and Warwickshire
Coventry, CV2 2DX, United Kingdom
Royal Infirmary of Edinburgh
Edinburgh, EH16 4TJ, United Kingdom
Royal Devon and Exeter NHS Trust
Exeter, PhD, United Kingdom
University Hospitals of Leicester NHS Trust
Leicester, LE1 7RH, United Kingdom
Royal Brompton Hospital
London, SWP 6NP, United Kingdom
Southampton General Hospital
Southampton, SO16 6YD, United Kingdom
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Robert Stockley, Prof.
University of Birmingham
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Double-blind
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 20, 2018
First Posted
August 17, 2018
Study Start
October 29, 2018
Primary Completion
March 2, 2022
Study Completion
March 30, 2022
Last Updated
April 14, 2022
Record last verified: 2022-04
Data Sharing
- IPD Sharing
- Will not share