Comparison of Pharmacokinetic, Safety, Tolerability of Alpha-1 MP and Prolastin In Alpha1-antitrypsin Deficient Adults

Phase 3

Completed

Brief Summary: 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.

Detailed Description: The objective of this study is to demonstrate the pharmacokinetic comparability of Alpha-1 MP to Prolastin® in subjects with Alpha1-antitrypsin deficiency.

This study is divided into three 8-week treatment sequences including an initial 8-week double-blind treatment period (with one of the 2 study drugs), a second 8-week double-blind treatment period (with the other study drug), and a third 8-week open-label treatment period (with Alpha-1 MP).

Recruitment & Eligibility

Inclusion Criteria

Documented diagnosis of congenital Alpha1-antitrypsin deficiency
Must be receiving augmentation therapy with plasma-derived (human) Alpha1-Proteinase Inhibitor (Prolastin®) for at least one month prior to study entry.
Signed written informed consent prior to initiation of any study related procedures

Exclusion Criteria

Females who are pregnant, breast feeding, or if of child-bearing potential, unwilling to practice adequate contraception throughout the study
Use of systemic steroids within the 2 weeks prior to receiving study treatment (this does not include the use of inhaled steroids used on a routine or as needed basis).
Subjects who have had exacerbations of their disease within one month of trial entry.

Arm && Interventions

Group	Intervention	Description
1 Alpha-1 MP	Alpha-1 MP	Sequential, blinded treatment periods of Alpha-1 MP (experimental), then crossed-over to Prolastin (active comparator), followed by open-label Alpha-1 MP
2 Prolastin	alpha-1 proteinase inhibitor (human)	Sequential, blinded treatment periods of Prolastin (active comparator), then crossed-over to Alpha-1 MP (experimental), followed by open-label Alpha-1 MP

Primary Outcome Measures

Name	Time	Method
Alpha-1 MP vs. Prolastin® of Area Under the Curve (AUC) From Day 0 to Day 7	Day 0 to Day 7	The primary objective of this study was to demonstrate the pharmacokinetic comparability (geometric least square mean ratio of AUC between the Alpha-1 MP vs. Prolastin®, 90% confidence interval falls within 0.80-1.25, FDA Guidance as being "bioequivalent" between two treatments) of Alpha-1 MP to Prolastin® in subjects with alpha-1-anti-trypsin (AAT) deficiency by comparing AUC from Day 0 to Day 7 of plasma Alpha1-PI measured by the functional activity (potency) assay. AUC from Day 0 to Day 7 was calculated at steady state at the end of the first and second 8-week treatment periods during the 16-week double-blind, crossover phase.

Secondary Outcome Measures

Name	Time	Method

Locations (8): National Jewish Medical and Research Center
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Denver, Colorado, United States
St Lukes-Roosevelt Hospital Center, New York
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New York, New York, United States
Cleveland Clinic Foundation
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Cleveland, Ohio, United States
Temple University Hospital
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Philadelphia, Pennsylvania, United States
University of Texas Health Center at Tyler
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Tyler, Texas, United States
University of Florida College of Medicine
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Gainesville, Florida, United States
University of Miami School of Medicine
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Miami, Florida, United States
Medical University of South Carolina
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Charleston, South Carolina, United States