Alpha1-Proteinase Inhibitor (Human), Aralast™, is a sterile, stable, lyophilized preparation of purified human alpha1-proteinase inhibitor ((alpha) 1-PI), also known as alpha1-antitrypsin.1
Alpha1-Proteinase Inhibitor (Human), Aralast™, is indicated for chronic augmentation therapy in patients having congenital deficiency of (alpha)1-PI with clinically evident emphysema. Clinical and biochemical studies have demonstrated that with such therapy, Aralast™ is effective in maintaining target serum (alpha)1-PI trough levels and increasing (alpha)1-PI levels in epithelial lining fluid (ELF). Clinical data demonstrating the long-term effects of chronic augmentation or replacement therapy of individuals with Aralast™ are not available.
Safety and effectiveness in pediatric patients have not been established. Aralast™ is not indicated as therapy for lung disease patients in whom congenital (alpha)1-PI deficiency has not been established.
Published Studies Related to Aralast ( 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 Aralast ( Alpha 1-Antitrypsin)
A Research Trial of Aralast in New Onset Diabetes (RETAIN) - Part I [Not yet recruiting]
The drug Alpha-1 Antitrypsin (AAT, Aralast NP), which is being tested in this clinical
trial,is an anti-inflammatory drug that affects the cells that are thought to be involved in
the development of type 1 diabetes. This trial, known as RETAIN, is a two-part trial to
investigate the effect of intravenous Alpha-1 Antitrypsin(AAT, Aralast NP) on preserving
beta cell function and to determine if AAT will help slow the progression of type 1
Part I of this clinical trial is an open-label, safety and dose level study consisting of
two groups. In Part I, all participants will receive the experimental drug and will be
tested to see if the drug is safe and well tolerated. Two groups of participants with
new-onset type 1 diabetes will be enrolled. After participants have completed the trial and
a satisfactory safety review is completed, enrollment in Part II (NCT#) of the study will
Pharmacokinetic Study of Aralast (Human Alpha1- PI) [Completed]
The primary purpose of this study is to characterize the pharmacokinetic profile of
intravenous Aralast Fraction (Fr.) IV-1, a sterile, stable, lyophilized preparation of
functionally intact human Alpha1- Proteinase Inhibitor (Alpha1-PI). This pharmacokinetic
study will be a randomized controlled clinical trial with a cross-over design. Twenty-four
subjects will be enrolled into the study. Overall study duration will be approximately 6-8
A Research Trial of Aralast in New Onset Diabetes (RETAIN) - Part II [Not yet recruiting]
The drug Alpha-1 Antitrypsin (AAT, Aralast NP), which is being tested in this clinical
trial, is an anti-inflammatory drug that affects the cells that are thought to be involved
in the development of type 1 diabetes. This trial, known as RETAIN, is a clinical trial is
a two-part trial investigating the effect of intravenous Alpha-1 Antitrypsin(AAT, Aralast
NP) on preserving beta cell function and to determine if AAT will help slow the progression
of type 1 diabetes.
Part I of this trial (NCT#) is an open-label, safety and dose level study consisting of two
groups. After Part I is completed, including a satisfactory safety review, enrollment in
Part II will begin. Part II is a two-arm, double-blind, placebo-controlled clinical trial,
and participants will be randomly assigned to either the treatment or placebo group.
Effect of Double Dose of Alpha 1-antitrypsin Augmentation Therapy on Lung Inflammation. [Recruiting]
The current treatment of individuals with alpha-1 antitrypsin deficiency (AATD) who develop
lung disease (COPD) is the administration of intravenous purified alpha-1 antitrypsin
(augmentation therapy) at a fixed dose of 60 mg/kg per week. This dose increases serum
levels just above a predetermined "safety threshold" of 11 uM. However, normal levels of AAT
are around 36 uM. AAT has shown not only to inhibit lung proteases such as neutrophil
elastase, but also to modulate inflammation.
Given that many subjects with AATD who receive augmentation therapy still have significant
lung disease and inflammation, this study will evaluate whether doubling the dose to 120
mg/kg/week has an effect in decreasing lung inflammation.
Only the dosing of 60 mg/kg /week has received FDA approval. FDA has granted an IND number
to this study to test the higher dose of 120 mg/kg/week.
The study will evaluate systemic (serum) and pulmonary (bronchoscopy samples)markers of
inflammation in 3 phases: standard dose (4 weeks), double dose (4 weeks) and standard dose
Aralast alpha1-Proteinase Inhibitor Surveillance Study [Active, not recruiting]
The primary objectives of this Phase 4, open label, prospective U. S. surveillance study are
to evaluate the health outcomes of AAT-deficient subjects who are initiating treatment with
ARALAST on patient-related outcomes (PRO), i. e., health-related quality of life (HRQoL),
healthcare resource utilization (HCRU), and various laboratory analyses to evaluate the
safety of long-term administration of ARALAST.
Up to 120 subjects will be enrolled and assessed for HRQoL and HCRU at baseline and every
6-months thereafter, for 2 years. A subset of subjects will be enrolled into the blood draw
portion of the study, which will also include assessments of antibodies to ARALAST, and
chemistry panel. Subjects will be treated according to the prescribing (attending)
physician's instructions based on the prescribing information given in the ARALAST package
Reports of Suspected Aralast ( Alpha 1-Antitrypsin) Side Effects
Abdominal Pain (1),
Pulmonary Mass (1),
Chronic Obstructive Pulmonary Disease (1),
Cardiac Disorder (1),
Liver Disorder (1),
Myocardial Infarction (1),
Alpha-1 Anti-Trypsin Deficiency (1), more >>
Page last updated: 2011-12-09