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Pharmacokinetic comparability of Prolastin®-C to Prolastin® in alpha₁-antitrypsin deficiency: a randomized study
James M Stocks1, Mark L Brantly, Laurene Wang-Smith
1Department of Medicine, University of Texas Health Science Center at Tyler, 75708-3154, USA. james.stocks@uthct.edu
Insights
New Prolastin-C, an alpha₁-proteinase inhibitor (API), is pharmacokinetically equivalent and as safe as the original Prolastin for treating alpha1-antitrypsin deficiency. This ensures effective augmentation therapy for patients with AAT deficiency.
Area of Science:
- Pharmacology
- Pulmonology
- Biotechnology
Background:
- Alpha1-antitrypsin (AAT) deficiency is a genetic disorder linked to emphysema due to low alpha1-proteinase inhibitor (alpha₁-PI) levels.
- Augmentation therapy using Prolastin® (alpha₁-PI) has been a standard treatment for AAT deficiency for over two decades.
- Prolastin®-C is a modified alpha₁-PI product with enhanced purification and pathogen-reduction steps.
Purpose of the Study:
- To assess the pharmacokinetic comparability of Prolastin®-C to the original Prolastin® in individuals with AAT deficiency.
- To evaluate the safety profile of Prolastin®-C in comparison to Prolastin®.
Main Methods:
- A randomized, crossover study involving 24 subjects with AAT deficiency.
- Subjects received weekly intravenous infusions of either Prolastin®-C or Prolastin® (60 mg/kg) for 8 weeks, followed by crossover to the alternate treatment for another 8 weeks.
- Pharmacokinetic analysis focused on the area under the plasma concentration versus time curve (AUC₀₋₇) of alpha₁-PI.
Main Results:
- Pharmacokinetic equivalence was demonstrated, with a mean AUC₀₋₇ of 155.9 mg*h/mL for Prolastin®-C versus 152.4 mg*h/mL for Prolastin®.
- The ratio of AUC₀₋₇ for Prolastin®-C to Prolastin® was 1.03 (90% CI: 0.97-1.09), confirming comparability.
- Adverse event rates were similar between treatments, and no treatment-emergent viral infections were reported.
Conclusions:
- Prolastin®-C is pharmacokinetically equivalent to Prolastin®.
- Prolastin®-C exhibits a comparable safety profile to Prolastin®.
- The modified Prolastin®-C offers a safe and effective alternative for augmentation therapy in AAT deficiency.
Background:
Alpha1-antitrypsin (AAT) deficiency is characterized by low blood levels of alpha1-proteinase inhibitor (alpha₁-PI) and may lead to emphysema. Alpha₁-PI protects pulmonary tissue from damage caused by the action of proteolytic enzymes. Augmentation therapy with Prolastin® (Alpha₁-Proteinase Inhibitor [Human]) to increase the levels of alpha₁-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 alpha₁-PI product, designated Prolastin®-C (Alpha₁-Proteinase inhibitor [Human]). The pharmacokinetic comparability of Prolastin-C to Prolastin was assessed in subjects with AAT deficiency.
Methods:
In total, 24 subjects were randomized to receive 60 mg/kg of functionally active Prolastin-C or Prolastin by weekly intravenous infusion for 8 weeks before crossover to the alternate treatment for another 8 weeks. Pharmacokinetic plasma samples were drawn over 7 days following last dose in the first treatment period and over 10 days following the last dose in the second period. The primary end point for pharmacokinetic comparability was area under the plasma concentration versus time curve over 7 days post dose (AUC₀₋₇ (days)) of alpha₁-PI determined by potency (functional activity) assay. The crossover phase was followed by an 8-week open-label treatment phase with Prolastin-C only.
Results:
Mean AUC₀₋₇ (days) was 155.9 versus 152.4 mg*h/mL for Prolastin-C and Prolastin, respectively. The geometric least squares mean ratio of AUC₀₋₇ (days) for Prolastin-C versus Prolastin had a point estimate of 1.03 and a 90% confidence interval of 0.97-1.09, demonstrating pharmacokinetic equivalence between the 2 products. Adverse events were similar for both treatments and occurred at a rate of 0.117 and 0.078 per infusion for Prolastin-C (double-blind treatment phase only) and Prolastin, respectively (p = 0.744). There were no treatment-emergent viral infections in any subject for human immunodeficiency virus, hepatitis B or C, or parvovirus B19 during the course of the study.
Conclusion:
Prolastin-C demonstrated pharmacokinetic equivalence and a comparable safety profile to Prolastin.
Trial Registration:
ClinicalTrials.gov Identifier: NCT00295061.
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