Alpha 1-Antitrypsin DeficiencyPhase 2ASTRAEUSNCT03636347
A 12-week Study Treating Participants Who Have alpha1-antitrypsin-related COPD With Alvelestat (MPH966) or Placebo.
A Phase 2 study testing Alvelestat oral tablet - dose 1 and Alvelestat oral tablet - dose 2 in people with Alpha 1-Antitrypsin Deficiency and Emphysema, run by Mereo BioPharma at 26 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Alpha 1-Antitrypsin Deficiency, Emphysema, COPD
- What is being tested?
- Alvelestat oral tablet - dose 1 and Alvelestat oral tablet - dose 2
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 99 participants
- Where
- 26 sitesin 8 countries
- Study dates
- 29 Oct 2018to 30 Mar 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
26 sites in 8 countries.
26 sites in 8 countries
United Kingdom8 sites
University Hospitals Birmingham NHS Foundation Trust
Birmingham, B15 2GW
Cambridge University Hospitals Foundation NHS Trust
Cambridge, CB2 0QQ
University Hospital Coventry and Warwickshire
Coventry, CV2 2DX
Royal Infirmary of Edinburgh
Edinburgh, EH16 4TJ
Royal Devon and Exeter NHS Trust
Exeter, PhD
University Hospitals of Leicester NHS Trust
Leicester, LE1 7RH
Royal Brompton Hospital
London, SWP 6NP
Southampton General Hospital
Southampton, SO16 6YD
United States4 sites
University of Alabama, Birmingham (UAB)
Birmingham, Alabama, 35294
UCLA Medical Center
Los Angeles, California, 90095
UC Davis Medical Centre
Sacramento, California, 95817
PMG Research of Wilmington
Wilmington, North Carolina, 28401
Canada4 sites
The University Lung Clinic
Edmonton, Alberta, T6G 2C8
University of Saskatchewan Royal University Hospital
Saskatoon, Saskatchewan, S7N 0W8
Inspiration Research Ltd
Toronto, Ontario, M5T 3A9
Centre for Heart Lung Innovation, St Pauls Hospital
Vancouver, British Columbia, V6Z 1Y6
Denmark3 sites
Aarhus Universitetshospital
Aarhus, 8200
Gentofte Hospital
Hellerup, 2900
Synddansk Universitet (SDU) - Odense University
Odense, 5000
Spain2 sites
Hospital Univ Clinico San Carlos
Madrid
Hospital Sierrallana
Torrelavega
Sweden2 sites
CTC Gothia Forum Sahlgrenska University Hospital
Gothenburg, 41345
Lund University Hospital
Lund, 22185
About this study
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.
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.
- Conditions
- Alpha 1-Antitrypsin Deficiency, Emphysema, COPD
- Being tested
- Placebo Oral Tablet, Alvelestat oral tablet - dose 1, Alvelestat oral tablet - dose 2
- Keywords
- PiZZ or Null, Neutrophil elastase inhibitor, Alpha-1, Alvelestat, AZD9668, MPH966, Rare variant genotype, Astraeus, AATD, Alpha 1-Antitrypsin Deficiency, Lung Disease
- Medical subject headings
- alpha 1-Antitrypsin Deficiency, Emphysema, Pulmonary Disease, Chronic Obstructive, Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo Oral TabletDrug
twice daily administration
Alvelestat oral tablet - dose 1Drug
Also called MPH966
twice daily administration
Alvelestat oral tablet - dose 2Drug
Also called MPH966
twice daily administration
| Study group | Role | What they receive |
|---|---|---|
| Placebo oral tablet | Placebo comparator | Not described Receives: Drug: Placebo Oral Tablet |
| Alvelestat oral tablet - dose 1 | Active comparator | MPH966 Receives: Drug: Alvelestat oral tablet - dose 1 |
| Alvelestat oral tablet - dose 2 | Active comparator | MPH966 Receives: Drug: Alvelestat oral tablet - dose 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 weeks
Secondary outcomes (1)
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
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2018
- Study start29 Oct 2018
- Primary completion2 Mar 2022
- Study completion30 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alpha 1-Antitrypsin DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- placebo-controlled, dose ascending, sequential group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mereo BioPharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Syneos Health
- Responsible party
- Sponsor
- Investigators
- Robert Stockley, Prof., Principal investigator, University of Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03636347
- Sponsor's protocol ID
- MPH966-2-01
- Other IDs
- 2018-001309-95, 2018
- Acronym
- ASTRAEUS
- Status last verified
- Apr 2022
- First submitted
- 20 Jun 2018
- Last updated
- 14 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT03636347
- Acronym / sponsor ID
- ASTRAEUS / MPH966-2-01
- Conditions
- Alpha 1-Antitrypsin Deficiency, Emphysema, COPD
- Keywords
- PiZZ or Null, Neutrophil elastase inhibitor, Alpha-1, Alvelestat, AZD9668, MPH966, Rare variant genotype, Astraeus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 99 participants (actual)
- Lead sponsor
- Mereo BioPharmaIndustry (pharma, biotech, devices)
- Collaborators
- Syneos Health
- Study start
- 29 Oct 2018 (actual)
- Primary completion
- 2 Mar 2022 (actual)
- Study completion
- 30 Mar 2022 (actual)
- First posted
- 17 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- placebo-controlled, dose ascending, sequential group
| Arm | Type | Receives |
|---|---|---|
| Placebo oral tablet | Placebo comparator | Drug: Placebo Oral Tablet |
| Alvelestat oral tablet - dose 1 | Active comparator | Drug: Alvelestat oral tablet - dose 1MPH966 |
| Alvelestat oral tablet - dose 2 | Active comparator | Drug: Alvelestat oral tablet - dose 2MPH966 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo Oral Tablettwice daily administration | Drug | Placebo oral tablet |
| Alvelestat oral tablet - dose 1Also: MPH966twice daily administration | Drug | Alvelestat oral tablet - dose 1 |
| Alvelestat oral tablet - dose 2Also: MPH966twice daily administration | Drug | Alvelestat oral tablet - dose 2 |
Primary outcome
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
1 secondary outcome
Change from baseline on other blood biomarkers of neutrophil elastase activity
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Stockley, Prof. principal investigator
University of Birmingham
26 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alvelestat oral tablet - dose 1 and Alvelestat oral tablet - dose 2 in people with Alpha 1-Antitrypsin Deficiency and Emphysema, run by Mereo BioPharma at 26 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United Kingdom, United States, Canada, Denmark, Belgium and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline on blood biomarkers of neutrophil elastase activity compared to baseline and placebo (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2022.