Clinical trial NCT03636347: A 12-week Study Treating Participants Who Have alpha1-antitrypsin-related COPD With Alvelestat (MPH966) or Placebo.
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Mereo BioPharma
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
First posted: 2018-08-17
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: placebo-controlled, dose ascending, sequential group
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change from baseline on blood biomarkers of neutrophil elastase activity compared to baseline and placebo
timeFrame: 12 weeks
Secondary outcomes:
measure: Change from baseline on other blood biomarkers of neutrophil elastase activity
timeFrame: 12 weeks
Other outcomes:
measure: Change from baseline in St. George's Respiratory Questionnaire (SGRQ-C) to end of treatment
timeFrame: 12 weeks
measure: Change from baseline in pulmonary function
timeFrame: 12 weeks
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham (UAB)
state: Alabama
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Centre
state: California
city: Wilmington
country: United States
facility: PMG Research of Wilmington
state: North Carolina
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Edmonton
country: Canada
facility: The University Lung Clinic
state: Alberta
city: Vancouver
country: Canada
facility: Centre for Heart Lung Innovation, St Pauls Hospital
state: British Columbia
city: Toronto
country: Canada
facility: Inspiration Research Ltd
state: Ontario
city: Saskatoon
country: Canada
facility: University of Saskatchewan Royal University Hospital
state: Saskatchewan
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital
city: Hellerup
country: Denmark
facility: Gentofte Hospital
city: Odense
country: Denmark
facility: Synddansk Universitet (SDU) - Odense University
city: Warsaw
country: Poland
facility: Instytut Gruzilicy Chorob Pluc
city: Madrid
country: Spain
facility: Hospital Univ Clinico San Carlos
city: Torrelavega
country: Spain
facility: Hospital Sierrallana
city: Gothenburg
country: Sweden
facility: CTC Gothia Forum Sahlgrenska University Hospital
city: Lund
country: Sweden
facility: Lund University Hospital
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals Foundation NHS Trust
city: Coventry
country: United Kingdom
facility: University Hospital Coventry and Warwickshire
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter NHS Trust
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: University of Birmingham
name: Robert Stockley, Prof.
role: PRINCIPAL_INVESTIGATOR
References: