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A 12-week Study Treating Participants Who Have alpha1-antitrypsin-related COPD With Alvelestat (MPH966) or Placebo. (ASTRAEUS)

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ClinicalTrials.gov Identifier: NCT03636347
Recruitment Status : Recruiting
First Posted : August 17, 2018
Last Update Posted : April 10, 2019
Sponsor:
Collaborator:
Syneos Health
Information provided by (Responsible Party):
Mereo BioPharma

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 or null 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.

Condition or disease Intervention/treatment Phase
Alpha 1-Antitrypsin Deficiency Emphysema COPD Drug: Placebo Oral Tablet Drug: Alvelestat oral tablet - dose 1 Drug: Alvelestat oral tablet - dose 2 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 165 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: placebo-controlled, dose ascending, sequential group
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-blind
Primary Purpose: Treatment
Official Title: 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 (PiZZ or Null) Antitrypsin Deficiency
Actual Study Start Date : October 31, 2018
Estimated Primary Completion Date : September 2, 2019
Estimated Study Completion Date : October 30, 2019


Arm Intervention/treatment
Placebo Comparator: Placebo oral tablet Drug: Placebo Oral Tablet
twice daily administration

Active Comparator: Alvelestat oral tablet - dose 1
MPH966
Drug: Alvelestat oral tablet - dose 1
twice daily administration
Other Name: MPH966

Active Comparator: Alvelestat oral tablet - dose 2
MPH966
Drug: Alvelestat oral tablet - dose 2
twice daily administration
Other Name: MPH966




Primary Outcome Measures :
  1. Change from baseline on blood biomarkers of neutrophil elastase activity [ Time Frame: 12 weeks ]
    Within-individual % change from baseline in plasma desmosine/isodesmosine at end of treatment compared to placebo


Secondary Outcome Measures :
  1. Change from baseline on other blood biomarkers of neutrophil elastase activity [ Time Frame: 12 weeks ]
    Overall change from baseline in plasma desmosine/isodesmosine


Other Outcome Measures:
  1. Change from baseline in St. George's Respiratory Questionnaire (SGRQ-C) at end of treatment [ Time Frame: 12 weeks ]
    Total score

  2. Change from baseline in pulmonary function [ Time Frame: 12 weeks ]
    Change from baseline in forced expiratory volume in 1 second (FEV1)



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a confirmed diagnosis of alpha-1-anti-trypsin deficiency and a PiZZ or null geno/phenotype and serum anti-alpha1 antitrypsin levels of less than 11uM
  • FEV1 ≥25% predicted
  • Computerised tomography (CT) scan evidence of emphysema
  • Non-smokers

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03636347


Contacts
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Contact: Ian Hodgson, PhD +44 (0)333 0237 300 enquiries@mereobiopharma.com
Contact: Jackie Parkin, MD enquiries@mereobiopharma.com

Locations
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United States, Alabama
University of Alabama, Birmingham (UAB) Recruiting
Birmingham, Alabama, United States, 35294
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
United States, California
UCLA Medical Center Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
UC Davis Medical Centre Not yet recruiting
Sacramento, California, United States, 95817
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
United States, North Carolina
PMG Research of Wilmington Recruiting
Wilmington, North Carolina, United States, 28401
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
Canada, Alberta
The University Lung Clinic Recruiting
Edmonton, Alberta, Canada, T6G 2C8
Contact: Ian Hodgson       enquiries@mereobiopharma.com   
Canada, British Columbia
Centre for Heart Lung Innovation, St Pauls Hospital Not yet recruiting
Vancouver, British Columbia, Canada, V6Z 1Y6
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
Canada, Ontario
Inspiration Research Ltd Recruiting
Toronto, Ontario, Canada, M5T 3A9
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
Canada, Saskatchewan
University of Saskatchewan Royal University Hospital Recruiting
Saskatoon, Saskatchewan, Canada, S7N 0W8
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
Denmark
Aarhus Universitetshospital Recruiting
Aarhus, Denmark, 8200
Contact: Ian Hodgson, PhD       Enquiries@mereobiopharma.com   
Gentofte Hospital Not yet recruiting
Hellerup, Denmark, 2900
Contact: Ian Hodgson       Enquiries@mereobiopharma.com   
Synddansk Universitet (SDU) - Odense University Recruiting
Odense, Denmark, 5000
Contact: Ian Hodgson       enquiries@mereobiopharma.com   
Poland
Instytut Gruzilicy Chorob Pluc Not yet recruiting
Warsaw, Poland, 01-138
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
Spain
Hospital Univ Clinico San Carlos Not yet recruiting
Madrid, Spain
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
Hospital Sierrallana Recruiting
Torrelavega, Spain
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
Sweden
CTC Gothia Forum Sahlgrenska University Hospital Recruiting
Gothenburg, Sweden, 41345
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
Lund University Hospital Recruiting
Lund, Sweden, 22185
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
United Kingdom
University Hospitals Birmingham NHS Foundation Trust Recruiting
Birmingham, United Kingdom, B15 2GW
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
Cambridge University Hospitals Foundation NHS Trust Recruiting
Cambridge, United Kingdom, CB2 0QQ
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
University Hospital Coventry and Warwickshire Not yet recruiting
Coventry, United Kingdom, CV2 2DX
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
Royal Infirmary of Edinburgh Recruiting
Edinburgh, United Kingdom, EH16 4TJ
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
Royal Devon and Exeter NHS Trust Not yet recruiting
Exeter, United Kingdom, PhD
Contact: Ian Hodgson       enquiries@mereobiopharma.com   
University Hospitals of Leicester NHS Trust Recruiting
Leicester, United Kingdom, LE1 7RH
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
Royal Brompton Hospital Recruiting
London, United Kingdom, SWP 6NP
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
Southampton General Hospital Recruiting
Southampton, United Kingdom, SO16 6YD
Contact: Ian Hodgson, PhD       enquiries@mereobiopharma.com   
Sponsors and Collaborators
Mereo BioPharma
Syneos Health
Investigators
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Principal Investigator: Robert Stockley, Prof. University of Birmingham

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Responsible Party: Mereo BioPharma
ClinicalTrials.gov Identifier: NCT03636347     History of Changes
Other Study ID Numbers: MPH966-2-01
2018-001309-95 ( EudraCT Number )
First Posted: August 17, 2018    Key Record Dates
Last Update Posted: April 10, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Mereo BioPharma:
PiZZ or Null genotype
Neutrophil elastase inhibitor
Alpha-1
Alvelestat
AZD9668
MPH966

Additional relevant MeSH terms:
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Emphysema
Alpha 1-Antitrypsin Deficiency
Pathologic Processes
Liver Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema
Alpha 1-Antitrypsin
Protein C Inhibitor
Trypsin Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action