DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Aralast ( Alpha 1-Antitrypsin) - Summary



ARALAST NP is a sterile, stable, lyophilized preparation of purified human alpha1–proteinase inhibitor (α1–PI), also known as alpha1–antitrypsin.1 ARALAST NP is a similar product to ARALAST, containing the same active components of plasma α1-PI with identical formulations. ARALAST NP is prepared from large pools of human plasma by using the cold ethanol fractionation process, followed by purification steps including polyethylene glycol and zinc chloride precipitations and ion exchange chromatography. All U.S. licensed α1-PI plasma derived products contain chemical modifications which arise during manufacturing and occur in varying levels from product to product.11 ARALAST NP contains approximately 2% α1-PI with truncated C-terminal lysine (removal of Lys394), whereas ARALAST contains approximately 67% α1-PI with the C-terminal lysine truncation.12 No known data suggest influence of these structural modifications on the functional activity and immunogenicity of α1-PI.13 To reduce the risk of viral transmission, the manufacturing process includes treatment with a solvent detergent (S/D) mixture [tri–n–butyl phosphate and polysorbate 80] to inactivate enveloped viral agents such as human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV). In addition, a nanofiltration step is incorporated into the manufacturing process to reduce the risk of transmission of enveloped and non–enveloped viral agents. Based on in vitro studies, the process used to produce ARALAST NP has been shown to inactivate and/or partition various viruses as shown in Table 1 below.2
Table 1: Virus Log Reduction in ARALAST NP Manufacturing Process
Processing Step Virus Log Reduction Factors
Cold ethanol fractionation 4.6 1.4 2.1 1.4 < 1.0 1
Solvent Detergent-treatment > 5.8 > 6.0 > 5.5 N/A 2 N/A
15 N nanofiltration > 5.3 > 6.0 > 5.6 > 5.1 4.9
Overall reduction factor > 15.7 > 13.4 > 13.2 > 6.5 4.9
HIV-1: Human immunodeficiency virus-1, BVDV (Bovine Viral Diarrhea Virus, model for Hepatitis C Virus and other lipid enveloped RNA viruses), PRV (Pseudorabies Virus, model for lipid-enveloped DNA viruses, to wich also hepatitis B belongs): HAV: Hepatitus A Virus, MMV (Mice Minute Virus, model for small non-lipid enveloped DNA viruses)

1 reduction factors ≤1.0 are not used for calculation of the overall reduction factor
2 Not applicable; study did not test for virus indicated

The unreconstituted, lyophilized cake should be white or off-white to slightly yellow-green or yellow in color. When reconstituted as directed, the concentration of functionally active α1–PI is ≥16 mg/mL and the specific activity is ≥0.55 mg active α1–PI/mg total protein. The composition of the reconstituted product is as follows:
Component Quality/mL
Elastase Inhibitory Activity ≥400 mg Active α1–PI/0.5 g vial*
≥800 mg Active α1–PI/1.0 g vial**
Albumin ≤5 mg/mL
Polyethylene Glycol ≤112 µg/mL
Polysorbate 80 ≤50 µg/mL
Sodium ≤230 mEq/L
Tri-n-buyl Phosphate ≤1.0 µg/mL
Zinc ≤3 ppm
* Reconstitution volume: 25mL/0.5 g vial
** Reconstitution volume: 50mL/1.0 g vial
Each vial of ARALAST NP is labeled with the amount of functionally active α1–PI expressed in mg/vial. The formulation contains no preservative. The pH of the solution ranges from 7.2 to 7.8. Product must only be administered intravenously.

Congenital Alpha–Proteinase Inhibitor deficiency

ARALAST NP is indicated for chronic augmentation therapy in patients having congenital deficiency of α1–PI with clinically evident emphysema. Clinical and biochemical studies have demonstrated that with such therapy, ARALAST is effective in maintaining target serum α1–PI trough levels and increasing α1–PI levels in epithelial lining fluid (ELF). ARALAST NP pharmacokinetics are comparable with the pharmacokinetics of ARALAST after single-dose administration in 25 subjects with congenital deficiency of α1–PI. Clinical data demonstrating the long–term effects of chronic augmentation or replacement therapy of individuals with ARALAST NP or ARALAST are not available.

The effect of augmentation therapy with ARALAST NP on pulmonary exacerbations and on the progression of emphysema in alpha1-antitrypsin deficiency has not been demonstrated in randomized, controlled clinical trials.

ARALAST NP is not indicated as therapy for lung disease patients in whom congenital α1–PI deficiency has not been established.

See all Aralast indications & dosage >>


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...

more studies >>

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 diabetes.

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 begin.

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 months.

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.

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 insert.

International Study Evaluating the Safety and Efficacy of Inhaled, Human, Alpha-1 Antitrypsin (AAT) in Alpha-1 Antitrypsin Deficient Patients With Emphysema [Recruiting]
This is a randomised , placebo controlled, double blind , multicentre, Phase II/III study evaluating the safety and efficacy of Kamada AAT for inhalation in patients with Emphysema caused by Alpha-1 Antitrypsin (AAT) deficiency.

more trials >>

Reports of Suspected Aralast ( Alpha 1-Antitrypsin) Side Effects

Death (5)Abdominal Pain (1)Asthma (1)Thrombosis (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

-- advertisement -- The American Red Cross
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2015