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

Primary Purpose

Alpha 1-Antitrypsin Deficiency, Emphysema, COPD

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo Oral Tablet
Alvelestat oral tablet - dose 1
Alvelestat oral tablet - dose 2
Sponsored by
Mereo BioPharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alpha 1-Antitrypsin Deficiency focused on measuring PiZZ or Null, Neutrophil elastase inhibitor, Alpha-1, Alvelestat, AZD9668, MPH966, Rare variant genotype, Astraeus, AATD, Alpha 1-Antitrypsin Deficiency, Lung Disease

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama, Birmingham (UAB)
  • UCLA Medical Center
  • UC Davis Medical Centre
  • PMG Research of Wilmington
  • UZ Gent
  • UZ Leuven
  • The University Lung Clinic
  • Centre for Heart Lung Innovation, St Pauls Hospital
  • Inspiration Research Ltd
  • University of Saskatchewan Royal University Hospital
  • Aarhus Universitetshospital
  • Gentofte Hospital
  • Synddansk Universitet (SDU) - Odense University
  • Instytut Gruzilicy Chorob Pluc
  • Hospital Univ Clinico San Carlos
  • Hospital Sierrallana
  • CTC Gothia Forum Sahlgrenska University Hospital
  • Lund University Hospital
  • University Hospitals Birmingham NHS Foundation Trust
  • Cambridge University Hospitals Foundation NHS Trust
  • University Hospital Coventry and Warwickshire
  • Royal Infirmary of Edinburgh
  • Royal Devon and Exeter NHS Trust
  • University Hospitals of Leicester NHS Trust
  • Royal Brompton Hospital
  • Southampton General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Active Comparator

Active Comparator

Arm Label

Placebo oral tablet

Alvelestat oral tablet - dose 1

Alvelestat oral tablet - dose 2

Arm Description

MPH966

MPH966

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
June 20, 2018
Last Updated
April 6, 2022
Sponsor
Mereo BioPharma
Collaborators
Syneos Health
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1. Study Identification

Unique Protocol Identification Number
NCT03636347
Brief Title
A 12-week Study Treating Participants Who Have alpha1-antitrypsin-related COPD With Alvelestat (MPH966) or Placebo.
Acronym
ASTRAEUS
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 Antitrypsin Deficiency.
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
October 29, 2018 (Actual)
Primary Completion Date
March 2, 2022 (Actual)
Study Completion Date
March 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mereo BioPharma
Collaborators
Syneos Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alpha 1-Antitrypsin Deficiency, Emphysema, COPD
Keywords
PiZZ or Null, Neutrophil elastase inhibitor, Alpha-1, Alvelestat, AZD9668, MPH966, Rare variant genotype, Astraeus, AATD, Alpha 1-Antitrypsin Deficiency, Lung Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
placebo-controlled, dose ascending, sequential group
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-blind
Allocation
Randomized
Enrollment
99 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo oral tablet
Arm Type
Placebo Comparator
Arm Title
Alvelestat oral tablet - dose 1
Arm Type
Active Comparator
Arm Description
MPH966
Arm Title
Alvelestat oral tablet - dose 2
Arm Type
Active Comparator
Arm Description
MPH966
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Intervention Description
twice daily administration
Intervention Type
Drug
Intervention Name(s)
Alvelestat oral tablet - dose 1
Other Intervention Name(s)
MPH966
Intervention Description
twice daily administration
Intervention Type
Drug
Intervention Name(s)
Alvelestat oral tablet - dose 2
Other Intervention Name(s)
MPH966
Intervention Description
twice daily administration
Primary Outcome Measure Information:
Title
Change from baseline on blood biomarkers of neutrophil elastase activity compared to baseline and placebo
Description
Within-individual change from baseline up to end of treatment in: Blood neutrophil elastase activity Blood Aα-Val 360 levels Plasma desmosine/isodesmosine levels
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Change from baseline on other blood biomarkers of neutrophil elastase activity
Description
Frequency of neutrophil elastase levels below the limit of detection from baseline to end of treatment
Time Frame
12 weeks
Other Pre-specified Outcome Measures:
Title
Change from baseline in St. George's Respiratory Questionnaire (SGRQ-C) to end of treatment
Description
Total score
Time Frame
12 weeks
Title
Change from baseline in pulmonary function
Description
Change from baseline in forced expiratory volume in 1 second (FEV1)
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Stockley, Prof.
Organizational Affiliation
University of Birmingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama, Birmingham (UAB)
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UC Davis Medical Centre
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
PMG Research of Wilmington
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28401
Country
United States
Facility Name
UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
The University Lung Clinic
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2C8
Country
Canada
Facility Name
Centre for Heart Lung Innovation, St Pauls Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 1Y6
Country
Canada
Facility Name
Inspiration Research Ltd
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 3A9
Country
Canada
Facility Name
University of Saskatchewan Royal University Hospital
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7N 0W8
Country
Canada
Facility Name
Aarhus Universitetshospital
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark
Facility Name
Gentofte Hospital
City
Hellerup
ZIP/Postal Code
2900
Country
Denmark
Facility Name
Synddansk Universitet (SDU) - Odense University
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Instytut Gruzilicy Chorob Pluc
City
Warsaw
ZIP/Postal Code
01-138
Country
Poland
Facility Name
Hospital Univ Clinico San Carlos
City
Madrid
Country
Spain
Facility Name
Hospital Sierrallana
City
Torrelavega
Country
Spain
Facility Name
CTC Gothia Forum Sahlgrenska University Hospital
City
Gothenburg
ZIP/Postal Code
41345
Country
Sweden
Facility Name
Lund University Hospital
City
Lund
ZIP/Postal Code
22185
Country
Sweden
Facility Name
University Hospitals Birmingham NHS Foundation Trust
City
Birmingham
ZIP/Postal Code
B15 2GW
Country
United Kingdom
Facility Name
Cambridge University Hospitals Foundation NHS Trust
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
University Hospital Coventry and Warwickshire
City
Coventry
ZIP/Postal Code
CV2 2DX
Country
United Kingdom
Facility Name
Royal Infirmary of Edinburgh
City
Edinburgh
ZIP/Postal Code
EH16 4TJ
Country
United Kingdom
Facility Name
Royal Devon and Exeter NHS Trust
City
Exeter
ZIP/Postal Code
PhD
Country
United Kingdom
Facility Name
University Hospitals of Leicester NHS Trust
City
Leicester
ZIP/Postal Code
LE1 7RH
Country
United Kingdom
Facility Name
Royal Brompton Hospital
City
London
ZIP/Postal Code
SWP 6NP
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.astraeus-alpha1.com
Description
Study Website

Learn more about this trial

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

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