Alpha-1-Antitrypsin (AAT) To Treat Emphysema In AAT-Deficient Patients (EXACTLE)

Grifols

Status and phase

Completed

Phase 2

Conditions

Alpha 1-Antitrypsin Deficiency

Treatments

Drug: Alpha1-Proteinase Inhibitor (Human)

Drug: Albumin (Human) 20%, United States Pharmacopeia (USP)

Study type

Interventional

Funder types

Industry

Identifiers

NCT00263887

100533

Details and patient eligibility

About

The goal of this trial was to explore the utility of evaluating emphysema progression through CT scans measuring lung density during a 2 year period of weekly infusions of either placebo or human alpha-1-antitrypsin (AAT; Prolastin®). Exacerbation data recorded in patient diaries were also collected. All efficacy data were analyzed for potential use in evaluating Prolastin efficacy in this and other clinical trials.

Full description

This is a one to one randomized, placebo-controlled, clinical, exploratory study with the aim of collecting information on possible clinical endpoints i.e., the progression of emphysema by lung density measurements with CT scan and frequency of exacerbations that could be used for a subsequent placebo controlled clinical trial. Progression of disease will be investigated in 80 patients with alpha-1-antitrypsin deficiency, who will be treated with human alpha-1-antitrypsin (AAT; Prolastin®) or placebo weekly for two years to analyze the effect of treatment on lung density and exacerbations. Targeted augmentation therapy with weekly infusions of Prolastin® will be a dose of 60 mg/kg body weight (range of 51.72 to 71.43 mg per kg body weight).

Therefore, this study focuses on several questions:

Is the 15th percentile point calculated by analysis of CT lung histograms a useful endpoint for clinical trials in AAT deficiency?
Is quantitation of exacerbations in AAT-deficient patients a useful endpoint for clinical trials in AAT deficiency?
Are there significant differences between the treatments in favor of Prolastin®?

Enrollment

77 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patient with pulmonary emphysema due to severe congenital AAT deficiency of phenotype protease inhibitor Z (PiZ) or other rare genotypes (not MS, MZ or SZ) and AAT serum level < 11 microns (µM) or < 80 mg/dL (status to be confirmed by phenotyping and genotyping)
Inspiratory capacity (VC - ERV) > 1.2 L and forced expiratory volume at one second (FEV1) < 80% of predicted value post bronchodilator
FEV1/VC < 70% of predicted value post-bronchodilator or transfer factor of carbon monoxide (KCO) < 80% of predicted value post-bronchodilator
History of at least one exacerbation in the past 2 years
Written informed consent

Exclusion criteria

FEV1 < 25% of predicted value post-bronchodilator
Augmentation therapy for more than one month with plasma-derived human alpha 1-antitrypsin (AAT) within the last 2 years
History of lung transplant
Any lung surgery within the past 2 years
On any thoracic surgery waiting list
Diagnosis of liver cirrhosis
Severe concomitant disease
Active pulmonary infection/exacerbations within the last month
Active smoking during the last 6 months or plasma positive for cotinine
Body weight < 42 kg or > 92 kg
Pregnancy or lactation
Women of child-bearing potential without adequate contraception