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.

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.

Study Overview

• Status: Completed
• Conditions: Emphysema; Alpha 1-Antitrypsin Deficiency; COPD
• Intervention / Treatment: Drug: Placebo Oral Tablet; Drug: Alvelestat oral tablet - dose 1; Drug: Alvelestat oral tablet - dose 2

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • UZ Gent
  • Leuven, Belgium, 3000
    • UZ Leuven
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2C8
      • The University Lung Clinic
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Centre for Heart Lung Innovation, St Pauls Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5T 3A9
      • Inspiration Research Ltd
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • University of Saskatchewan Royal University Hospital
• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus Universitetshospital
  • Hellerup, Denmark, 2900
    • Gentofte Hospital
  • Odense, Denmark, 5000
    • Synddansk Universitet (SDU) - Odense University
• Poland
  • Warsaw, Poland, 01-138
    • Instytut Gruzilicy Chorob Pluc
• Spain
  • Madrid, Spain
    • Hospital Univ Clinico San Carlos
  • Torrelavega, Spain
    • Hospital Sierrallana
• Sweden
  • Gothenburg, Sweden, 41345
    • CTC Gothia Forum Sahlgrenska University Hospital
  • Lund, Sweden, 22185
    • Lund University Hospital
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • University Hospitals Birmingham NHS Foundation Trust
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals Foundation NHS Trust
  • Coventry, United Kingdom, CV2 2DX
    • University Hospital Coventry and Warwickshire
  • Edinburgh, United Kingdom, EH16 4TJ
    • Royal Infirmary of Edinburgh
  • Exeter, United Kingdom, PhD
    • Royal Devon and Exeter NHS Trust
  • Leicester, United Kingdom, LE1 7RH
    • University Hospitals of Leicester NHS Trust
  • London, United Kingdom, SWP 6NP
    • Royal Brompton Hospital
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama, Birmingham (UAB)
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis Medical Centre
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Alvelestat oral tablet - dose 1; MPH966	Drug: Alvelestat oral tablet - dose 1; twice daily administration; Other Names: MPH966
Active Comparator: Alvelestat oral tablet - dose 2; MPH966	Drug: Alvelestat oral tablet - dose 2; twice daily administration; Other Names: MPH966
Placebo Comparator: Placebo oral tablet	Drug: Placebo Oral Tablet; twice daily administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline on other blood biomarkers of neutrophil elastase activity	Frequency of neutrophil elastase levels below the limit of detection from baseline to end of treatment	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in St. George's Respiratory Questionnaire (SGRQ-C) to end of treatment	Total score	12 weeks
Change from baseline in pulmonary function	Change from baseline in forced expiratory volume in 1 second (FEV1)	12 weeks

Collaborators and Investigators

• Sponsor: Mereo BioPharma
• Collaborators: Syneos Health
• Investigators: Principal Investigator: Robert Stockley, Prof., University of Birmingham

Publications and helpful links

Helpful Links

• Study Website

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2018
• Primary Completion (Actual): March 2, 2022
• Study Completion (Actual): March 30, 2022

Study Registration Dates

• First Submitted: June 20, 2018
• First Submitted That Met QC Criteria: August 15, 2018
• First Posted (Actual): August 17, 2018

Study Record Updates

• Last Update Posted (Actual): April 14, 2022
• Last Update Submitted That Met QC Criteria: April 6, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Lung Disease; AATD; Alpha-1; Alpha 1-Antitrypsin Deficiency; Alvelestat; Neutrophil elastase inhibitor; PiZZ or Null; AZD9668; MPH966; Rare variant genotype; Astraeus
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Liver Diseases; Genetic Diseases, Inborn; Subcutaneous Emphysema; Emphysema; Alpha 1-Antitrypsin Deficiency
• Other Study ID Numbers: MPH966-2-01; 2018-001309-95 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No