NCT03679598

Alvelestat (MPH966) for the Treatment of ALpha-1 ANTitrypsin Deficiency

A First in Class Disease Modifying Therapy to Treat Alpha-1 Antitrypsin Deficiency a Genetically Linked Orphan Disease

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 63 (actual)
• Sponsor: University of Alabama at Birmingham · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 2, multicenter, double-blind, randomized (1:1), placebo-controlled, 12-week, proof-of-concept study to evaluate the safety and tolerability as well as the mechanistic effect of oral administration of alvelestat (MPH966) in subjects with confirmed AATD defined as Pi\*ZZ, Pi\*SZ, Pi\*null, or another rare phenotype/genotype known to be associated with either low (serum AAT level \<11 μM or \<57.2 mg/dL) or functionally impaired AAT including "F" or "I" mutations.

Detailed description

Alpha-1 antitrypsin deficiency (AATD) is the most common genetic cause of chronic obstructive pulmonary disease (COPD) and early-onset emphysema. AATD is characterized by low AAT levels; leading to excessive neutrophil elastase (NE) mediated lung destruction. Current treatment requires the periodic infusion of pooled AAT derived from human plasma, but this therapeutic approach (termed augmentation) does not definitively slow the rate of emphysema progressionlung function decline and is very expensive. In addition, it is not clear that the currently recommended dose for augmentation fully controls lung inflammation and destruction. Alvelestat (MPH966, formerly AZD9668) is a potent, selective, and reversible, oral inhibitor of human NE. Suppression of NE is expected to reduce lung damage and may slow disease progression. This study is to establish proof of clinical concept by investigating the mechanistic effect and safety of alvelestat (MPH966) in patients with AATD.

Conditions

• Alpha-1 Antitrypsin Deficiency (AATD)
• Pi*ZZ, Pi*SZ, Pi*Null, Another Rare Phenotype/Genotype Known to be Associated With Either Low or Functionally Impaired AAT Including F or I Mutations
• Emphysema or COPD

Interventions

Type	Name	Description
DRUG	Alvelestat (MPH966)	Alvelestat was developed as treatment for lung diseases like Chronic Obstructive Pulmonary Disease. Alevelestat works by blocking certain proteins in the body that are responsible for inflammation and damage to the lungs that can lead to COPD symptoms.
OTHER	Placebo	Placebo is a pill or tablet that does not contain any study drug.

Timeline

• Start date: 2019-04-08
• Primary completion: 2023-11-30
• Completion: 2023-12-01
• First posted: 2018-09-20
• Last updated: 2024-08-20
• Results posted: 2024-07-09

Locations

10 sites across 1 country: United States

Regulatory

• FDA-regulated drug study