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

• ClinicalTrials.gov Identifier: NCT00295061
• Recruitment Status: Completed
• First Posted: February 22, 2006
• Results First Posted: September 9, 2014
• Last Update Posted: September 9, 2014
• Sponsor: Grifols Therapeutics LLC
• Information provided by: Grifols Therapeutics LLC

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Alpha 1-Antitrypsin Deficiency	Drug: Alpha-1 MP; Drug: alpha-1 proteinase inhibitor (human)	Phase 3

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Multi-center, Randomized, Double-blind, Crossover Trial to Evaluate the Pharmacokinetic Comparability of Alpha-1 MP to Prolastin in Subjects With Alpha1-antitrypsin Deficiency.
• Study Start Date: May 2006
• Actual Primary Completion Date: February 2007
• Actual Study Completion Date: February 2007

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 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	Drug: Alpha-1 MP; alpha-1 proteinase inhibitor (human), 60 mg/kg body weight; Other Names: Alpha-1 antitrypsin (AAT); TAL6004
Active Comparator: 2 Prolastin; 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); Prolastin; Other Names: Alpha-1 antitrypsin (AAT); BAY x 5747; BAY 10-5233; TAL-05-00007

Outcome Measures

Primary Outcome Measures :

1. Alpha-1 MP vs. Prolastin® of Area Under the Curve (AUC) From Day 0 to Day 7 [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Colorado

National Jewish Medical and Research Center

Denver, Colorado, United States, 80206

United States, Florida

University of Florida College of Medicine

Gainesville, Florida, United States, 32610-0225

University of Miami School of Medicine

Miami, Florida, United States, 33101

United States, New York

St Lukes-Roosevelt Hospital Center, New York

New York, New York, United States, 10019

United States, Ohio

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44122

United States, Pennsylvania

Temple University Hospital

Philadelphia, Pennsylvania, United States, 19140

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

United States, Texas

University of Texas Health Center at Tyler

Tyler, Texas, United States, 75708-3154

Sponsors and Collaborators

Grifols Therapeutics LLC

Investigators

• Study Director: Kim Hanna, MSc; Grifols Therapeutics LLC

More Information

Additional Information:

The "Alpha-1 Foundation", dedicated to providing the leadership and resources that will result in increased research, improved health, worldwide detection and a cure for Alpha-1 Antitrypsin Deficiency 

AlphaNet, Inc devoted to improving the lives of individuals with Alpha-1 antitrypsin deficiency through comprehensive disease management services, clinical research administration, and consultative services 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Stocks JM, Brantly ML, Wang-Smith L, Campos MA, Chapman KR, Kueppers F, Sandhaus RA, Strange C, Turino G. Pharmacokinetic comparability of Prolastin®-C to Prolastin® in alpha₁-antitrypsin deficiency: a randomized study. BMC Clin Pharmacol. 2010 Sep 30;10:13. doi: 10.1186/1472-6904-10-13.

• Responsible Party: Gerald Klein, MD, Chief Medical Officer, Vice President of Medical and Clinical Affairs, Talecris Biotherapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT00295061
• Other Study ID Numbers: 11816
• First Posted: February 22, 2006
• Results First Posted: September 9, 2014
• Last Update Posted: September 9, 2014
• Last Verified: August 2014

Keywords provided by Grifols Therapeutics LLC:

alpha 1-Antitrypsin Deficiency; alpha 1-Antitrypsin; pulmonary emphysema

Additional relevant MeSH terms:

Alpha 1-Antitrypsin Deficiency; Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Protease Inhibitors; Alpha 1-Antitrypsin; Protein C Inhibitor; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Trypsin Inhibitors; Serine Proteinase Inhibitors