A Phase 2 Study to evaluate the effectiveness of Alvelestat (MPH966)
Research type
Research Study
Full 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.
IRAS ID
252196
Contact name
Robert Stockley
Contact email
Sponsor organisation
Mereo BioPharma 4 Ltd
Eudract number
2018-001309-95
Duration of Study in the UK
1 years, 2 months, 0 days
Research summary
This clinical study aims to investigate whether taking 120 mg or 240 mg of alvelestat twice daily is safe and likely to improve Alpha-1 antitrypsin deficiency (AATD)-lung disease by controlling elastase an inflammatory neutrophil enzyme which digests elastin in the lung tissue. Patients with AATD-lung disease lack the protein that normally control elastase and may experience progressive lung damage such as emphysema . We plan to measure whether the elastase is being controlled by measuring different parameters (markers) in the blood and sputum (phlegm or mucus), in particular desmosine which is a breakdown product of elastin which is elevated in AATD. We also plan to measure whether controlling the elastase with alvelestat affects symptoms of Alpha-1 antitrypsin deficiency such as breathing. Patients in the study will be closely monitored for safety through blood tests and clinical assessments.
Two doses of alvelestat (MPH966), 120 mg and 240 mg taken twice daily, will be tested against placebo (containing no active drug). Alvelestat and placebo are small white pills which are taken with water twice a day. The participant will be asked to take 8 pills in the morning and 8 pills in the evening, 12 hours apart. These doses are based on testing of alvelestat levels and neutrophil elastase suppression (Pharmacokinetics and Pharmacodynamics) modelling of alvelestat (MPH966). The participants will be those patients with the most severe Alpha-1 antitrypsin deficiency (either PiZZ or nulls) who have very low levels of the normal protective protein and with established lung disease (emphysema). This will enable the study to have sensitivity to detect a mechanistic signal for proof of concept, to support decisions about further development of alvelestat for this disease in combination with the safety information.
Following a screening period of up to 28 days, patients will be dosed with study treatment or placebo for 12 weeks, with a subsequent 4-week follow-up period for safety and determination of time to loss of of mechanistic effect on the primary endpoint (desmosine).
This study will be the first time that patients with Alpha-1 antitrypsin deficiency are dosed with alvelestat (MPH966), including doses with a small pool of patient experience and limited clinical safety data. For these reasons, the treatment period will include a phased dose-escalation approach, with defined safety decision points made by an independent Data Monitoring Committee (DMC) review.
REC name
London - West London & GTAC Research Ethics Committee
REC reference
18/LO/1706
Date of REC Opinion
30 Nov 2018
REC opinion
Further Information Favourable Opinion