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

Study Overview
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Brief Summary
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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
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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).

Official Title
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Multi-center, Randomized, Double-blind, Crossover Trial to Evaluate the Pharmacokinetic Comparability of Alpha-1 MP to Prolastin in Subjects With Alpha1-antitrypsin Deficiency.

Conditions
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Alpha 1-Antitrypsin Deficiency

Intervention / Treatment
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* Drug: Alpha-1 MP
* Drug: alpha-1 proteinase inhibitor (human)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 Alpha-1 MP<br>Sequential, blinded treatment periods of Alpha-1 MP (experimental), then crossed-over to Prolastin (active comparator), followed by open-label Alpha-1 MP | Drug: Alpha-1 MP<br>* alpha-1 proteinase inhibitor (human), 60 mg/kg body weight<br>* Other names: TAL6004;|
| Active Comparator: 2 Prolastin<br>Sequential, blinded treatment periods of Prolastin (active comparator), then crossed-over to Alpha-1 MP (experimental), followed by open-label Alpha-1 MP | Drug: alpha-1 proteinase inhibitor (human)<br>* Prolastin<br>* Other names: TAL-05-00007;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alpha-1 MP vs. Prolastin® of Area Under the Curve (AUC) From 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. | Day 0 to Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alpha 1-Antitrypsin Deficiency, alpha 1-Antitrypsin, pulmonary emphysema