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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03636347
Recruitment Status : Completed
First Posted : August 17, 2018
Last Update Posted : April 14, 2022
Sponsor:
Collaborator:
Syneos Health
Information provided by (Responsible Party):
Mereo BioPharma

Study Description
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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.

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

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 99 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 Antitrypsin Deficiency.
Actual Study Start Date : October 29, 2018
Actual Primary Completion Date : March 2, 2022
Actual Study Completion Date : March 30, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. Change from baseline on blood biomarkers of neutrophil elastase activity compared to baseline and placebo [ Time Frame: 12 weeks ]

    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 :
  1. Change from baseline on other blood biomarkers of neutrophil elastase activity [ Time Frame: 12 weeks ]
    Frequency of neutrophil elastase levels below the limit of detection from baseline to end of treatment


Other Outcome Measures:
  1. Change from baseline in St. George's Respiratory Questionnaire (SGRQ-C) to 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)


Eligibility Criteria
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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, 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
Contacts and Locations
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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


Locations
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Sponsors and Collaborators
Mereo BioPharma
Syneos Health
Investigators
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Principal Investigator: Robert Stockley, Prof. University of Birmingham
More Information
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Additional Information:

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Responsible Party: Mereo BioPharma
ClinicalTrials.gov Identifier: NCT03636347    
Other Study ID Numbers: MPH966-2-01
2018-001309-95 ( EudraCT Number )
First Posted: August 17, 2018    Key Record Dates
Last Update Posted: April 14, 2022
Last Verified: April 2022
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
Neutrophil elastase inhibitor
Alpha-1
Alvelestat
AZD9668
MPH966
 Rare variant genotype
Astraeus
AATD
Alpha 1-Antitrypsin Deficiency
Lung Disease
Additional relevant MeSH terms:
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Alpha 1-Antitrypsin Deficiency
Emphysema
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
 Liver Diseases
Digestive System Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema