Alpha1-Proteinase Inhibitor (Human), Prolastin® is a sterile, stable, lyophilized preparation of purified human Alpha1-Proteinase Inhibitor (alpha1-PI), also known as alpha1-antitrypsin. Prolastin is intended for use in therapy of congenital alpha1-antitrypsin deficiency.
Alpha1-Proteinase Inhibitor (Human), Prolastin® is indicated for chronic replacement therapy of individuals having congenital deficiency of alpha1-PI (alpha1-antitrypsin deficiency) with clinically demonstrable panacinar emphysema. Clinical and biochemical studies have demonstrated that with such therapy, it is possible to increase plasma levels of alpha1-PI, and that levels of functionally active alpha1-PI in the lung epithelial lining fluid are increased proportionately. 18-20 As some individuals with alpha1-antitrypsin deficiency will not go on to develop panacinar emphysema, only those with evidence of such disease should be considered for chronic replacement therapy with Prolastin. 22 Subjects with the PiMZ or PiMS phenotypes of alpha1-antitrypsin deficiency should not be considered for such treatment as they appear to be at small risk for panacinar emphysema. 22 Clinical data are not available as to the long-term effects derived from chronic replacement therapy of individuals with alpha1-antitrypsin deficiency with Prolastin. Only adult subjects have received Prolastin to date.
Prolastin is not indicated for use in patients other than those with PiZZ, PiZ(null) or Pi(null)(null) phenotypes.
Published Studies Related to Prolastin (Alpha 1-Antitrypsin)
The fibrinogen cleavage product Aalpha-Val360, a specific marker of neutrophil elastase activity in vivo. [2011.08]
BACKGROUND: Alpha-1-antitrypsin (A1AT) deficiency is the only recognised genetic risk factor for chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality worldwide. Since A1AT is the major inhibitor of neutrophil elastase (NE), this enzyme has become widely implicated in the pathogenesis of COPD in general; however, there is currently no specific biomarker for its pre-inhibition activity. Such a biomarker should be a measure of elastase-specific COPD disease activity with the potential to assess early targeted therapeutic intervention, in contrast to traditional and non-specific disease severity markers such as forced expiratory volume in 1 s... CONCLUSIONS: Aalpha-Val(360) represents the first specific footprint of pre-inhibition NE activity and is a potential biomarker of disease activity and progression in subjects with elastase-dependent COPD. TRIAL REGISTRATION: The EXACTLE study was registered in ClinicalTrials.gov as 'Antitrypsin (AAT) to Treat Emphysema in AAT-Deficient Patients'; ClinicalTrials.gov Identifier: NCT00263887.
Retinoid treatment of Emphysema in Patients on the Alpha-1 International Registry. The REPAIR study: study design, methodology and quality control of study assessments. [2010.12]
Emphysema is characterized by the destruction of alveolar wall and enlargement of alveolar airspaces, resulting in a reduction of the total lung gas exchange area, loss of lung elastic recoil and hyperinflation. The REPAIR study (Retinoid treatment of Emphysema in Patients on the Alpha-1 International Registry) is the first proof-of-concept study of a new potential disease-modifying drug, Palovarotene(c), an orally active, gamma selective retinoid agonist in patients with emphysema secondary to alpha-1-antitrypsin deficiency (AATD) as a model population for the general smoke-induced emphysema population.
Pharmacokinetic comparability of Prolastin(R)-C to Prolastin(R) in alpha-antitrypsin deficiency: a randomized study. [2010.09.30]
BACKGROUND: Alpha1-antitrypsin (AAT) deficiency is characterized by low blood levels of alpha1-proteinase inhibitor (alpha-PI) and may lead to emphysema. Alpha-PI protects pulmonary tissue from damage caused by the action of proteolytic enzymes. Augmentation therapy with Prolastin(R) (Alpha-Proteinase Inhibitor [Human]) to increase the levels of alpha-PI has been used to treat individuals with AAT deficiency for over 20 years. Modifications to the Prolastin manufacturing process, incorporating additional purification and pathogen-reduction steps, have led to the development of an alpha-PI product, designated Prolastin(R)-C (Alpha-Proteinase inhibitor [Human]). The pharmacokinetic comparability of Prolastin-C to Prolastin was assessed in subjects with AAT deficiency... CONCLUSION: Prolastin-C demonstrated pharmacokinetic equivalence and a comparable safety profile to Prolastin. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00295061.
Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha1-antitrypsin deficiency. [2009.06]
Assessment of emphysema-modifying therapy is difficult, but newer outcome measures offer advantages over traditional methods. The EXAcerbations and Computed Tomography scan as Lung End-points (EXACTLE) trial explored the use of computed tomography (CT) densitometry and exacerbations for the assessment of the therapeutic effect of augmentation therapy in subjects with alpha(1)-antitrypsin (alpha(1)-AT) deficiency...
Prevalence of alpha-1 antitrypsin deficiency in poorly controlled asthma--results from the ALA-ACRC low-dose theophylline trial. [2007.10]
In a study comparing low-dose theophylline to montelukast in poorly controlled asthmatics, 285 subjects consented to be screened for alpha-1 antitrypsin deficiency. Of the 284 for which complete data was available, 10.5% carried a deficiency gene and 2.4% were mildly deficient with an alpha-1 antitrypsin serum level of less than 20 mu M...
Clinical Trials Related to Prolastin (Alpha 1-Antitrypsin)
Safety and Pharmacokinetics of Alpha-1 Proteinase Inhibitor in Subjects With Alpha1-Antitrypsin Deficiency [Completed]
This is a study to assess the safety and pharmacokinetics of weekly infusions of 120 mg/kg
of Prolastin-C (alpha1-proteinase inhibitor [alpha1-PI] [Human]), compared to weekly
infusions of 60 mg/kg of Prolastin-C in patients with alpha 1-antitrypsin deficiency (AATD).
Comparison of Pharmacokinetic, Safety, Tolerability of Alpha-1 MP and Prolastin In Alpha1-antitrypsin Deficient Adults [Completed]
The purpose of this clinical study (ChAMP - Comparability pharmacokinetics of Alpha-1
Modified Process) is to compare the pharmacokinetic, safety and tolerability of Alpha-1
Proteinase Inhibitor (Human), modified process (Alpha-1 MP) and Prolastin in adult
Alpha1-antitrypsin deficient patients. Patients will be infused intravenously with study
drug on a weekly schedule for 24 weeks.
Alpha-1-Antitrypsin (AAT) To Treat Emphysema In AAT-Deficient Patients (EXACTLE) [Completed]
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.
A Research Trial of Aralast NP in New Onset Diabetes (RETAIN) - Part II [Withdrawn]
Aralast NP (alpha-1 antitrypsin, AAT), an alpha-1 proteinase inhibitor (human), was the drug
to be tested in this clinical trial. Aralast NP is an anti-inflammatory drug that affects
the cells that are thought to be involved in the development of type 1 diabetes mellitus
(T1DM, T1D). This study, known as RETAIN, was planned as a two-part trial to investigate the
effect of Aralast NP on preserving beta cell function and to determine if the intervention
would slow the progression of type 1 diabetes.
Part I of this trial (NCT 01183468) was an open-label, safety and dose level study
consisting of two groups. After completion of Part I, including a satisfactory safety
review, enrollment in Part II was to begin. Part II was designed as a two-arm,
double-blind, placebo-controlled clinical trial, and participants were to be randomly
assigned to either the Aralast NP treatment or placebo group.
Alpha1 Antitrypsin Aerosol Therapy in Cystic Fibrosis [Terminated]
The hypothesis being tested is that inhibition of the enzyme known as elastase in the
airways of patients with cystic fibrosis will help decrease the number of bacteria. Alpha1
antitrypsin, an elastase inhibitor, will be given to patients with cystic fibrosis by
aerosol therapy twice in 1 day and sputum will be collected to measure the density of
Reports of Suspected Prolastin (Alpha 1-Antitrypsin) Side Effects
Anaphylactic Shock (2),
Influenza Like Illness (2),
Infusion Related Reaction (2),
Drug Hypersensitivity (2),
Dermatitis Allergic (1),
Urticaria (1), more >>
Page last updated: 2011-12-09