Safety and Pharmacokinetics of Alpha-1 Proteinase Inhibitor in Subjects With Alpha1-Antitrypsin Deficiency

NCT ID: NCT01213043

Last Updated: 2013-05-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2012-01-31

Brief Summary

This is a study to assess the safety and pharmacokinetics of weekly infusions of 120 mg/kg of Prolastin-C (alpha1-proteinase inhibitor [alpha1-PI] [Human]), compared to weekly infusions of 60 mg/kg of Prolastin-C in patients with alpha 1-antitrypsin deficiency (AATD).

Detailed Description

The question of whether higher doses of alpha1-PI (>60 mg/kg) are able to provide better protection to patients with alpha 1-antitrypsin deficiency is currently unknown. As a first step to address this question, the present study has been undertaken. This is a multi-center, randomized, double-blind, crossover study to assess the safety and pharmacokinetics of weekly infusions of 120 mg/kg of Prolastin-C, compared to weekly infusions of 60 mg/kg of Prolastin-C in patients with alpha 1-antitrypsin deficiency. This study is a crossover design with 2 treatment sequences:

Treatment Sequence 1: 60 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 120 mg/kg weekly infusion of Prolastin-C for 8 weeks (starting at Week 1) (total of 16 treatment weeks)

Treatment Sequence 2: 120 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 60 mg/kg weekly infusion of Prolastin-C for 8 weeks (starting at Week 11) (total of 16 treatment weeks)

Approximately 15 subjects are planned to be entered into each treatment sequence.

At Weeks 8 to 11 and Weeks 18 to 21, a total of 15 serial blood samples for each subject will be drawn for pharmacokinetic analysis. The expected duration of the study subject's participation will be approximately 25 weeks (which includes a 3-Week Screening Phase, 2-Week Washout Period [between different alpha-1 PI treatment doses], and a 4-Week Follow-up Period). The following safety parameters will be assessed: adverse events, pulmonary exacerbations, vital signs, pulmonary function tests, and clinical laboratory tests.

Conditions

Emphysema; Alpha 1-antitrypsin Deficiency (AATD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Prolastin-C, 60 mg/kg

60 mg/kg weekly infusion of Prolastin-C for 8 weeks. Subjects were infused with 60 mg/kg Prolastin-C by means of one of two possible treatment sequences: 1) 60 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 120 mg/kg Prolastin-C for 8 weeks, or 2) 120 mg/kg Prolastin-C for 8 weeks followed by 60 mg/kg weekly infusion of Prolastin-C for 8 weeks (total of 16 weeks).

Group Type: ACTIVE_COMPARATOR

Prolastin-C, 60 mg/kg

Intervention Type: BIOLOGICAL

60 mg/kg weekly infusion of Prolastin-C for 8 weeks

Prolastin-C, 120 mg/kg

120 mg/kg weekly infusion of Prolastin-C for 8 weeks. Subjects were infused with 120 mg/kg Prolastin-C by means of one of two possible treatment sequences: 1) 60 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 120 mg/kg Prolastin-C for 8 weeks, or 2) 120 mg/kg Prolastin-C for 8 weeks followed by 60 mg/kg weekly infusion of Prolastin-C for 8 weeks (total of 16 weeks).

Group Type: EXPERIMENTAL

Prolastin-C, 120 mg/kg

Intervention Type: BIOLOGICAL

120 mg/kg weekly infusion of Prolastin-C for 8 weeks

Interventions

Prolastin-C, 60 mg/kg

60 mg/kg weekly infusion of Prolastin-C for 8 weeks

Intervention Type: BIOLOGICAL

Prolastin-C, 120 mg/kg

120 mg/kg weekly infusion of Prolastin-C for 8 weeks

Intervention Type: BIOLOGICAL

Other Intervention Names

Alpha1-Proteinase Inhibitor; Alpha1-Proteinase Inhibitor (Human), Modified Process; Alpha-1 MP; Alpha1-Proteinase Inhibitor; Alpha1-Proteinase Inhibitor (Human), Modified Process; Alpha-1 MP

Eligibility Criteria

Inclusion Criteria

• Be between 18 and 70 years of age
• Have a documented diagnosis of congenital AATD
• Have a post-bronchodilator Forced Expired Volume in 1 second (FEV1) of ≥30% and <80% and FEV1/forced vital capacity (FVC) <70%
• If receiving alpha-1 PI augmentation therapy, be willing to discontinue the treatment for the duration of the study

Exclusion Criteria

• Had a moderate or severe pulmonary exacerbation during the 4 weeks before the study
• History of lung or liver transplant
• Any lung surgery during the past 2 years
• Confirmed liver cirrhosis
• Elevated liver enzymes
• Severe concurrent disease
• Females who are pregnant or breast-feeding or unwilling to practice effective contraception during the study
• Infection with hepatitis A, B, or C, human immunodeficiency or parvovirus B19
• Smoking during the past 6 months
• Use of systemic steroids within 4 weeks of the study
• Use of antibiotics for an exacerbation within 4 weeks of the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grifols Therapeutics LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Brantly, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Michael Campos, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Friedrich Kueppers, MD

Role: PRINCIPAL_INVESTIGATOR

Temple University Hospital/Temple Lung Center

James Stocks, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center at Tyler

Charlie Strange, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina, Division of Pulmonary and Critical Care Medicine

Locations

University of Florida College of Medicine

Gainesville, Florida, United States

University of Miami

Miami, Florida, United States

Temple University Hosptial/Temple Lung Center

Philadelphia, Pennsylvania, United States

Medical University of South Carolina, Division of Pulmonary and Critical Care Medicine

Charleston, South Carolina, United States

The University of Texas Health Science Center at Tyler

Tyler, Texas, United States

Countries

United States

References

Willis T, Wee K, Mohn G. A high-purity Alpha-1 proteinase inhibitor from human plasma, TAL6004. Proceeding of the 19th European Respiratory Society Annual Congress; 2009 Sep 12-16; Vienna, Austria. Abstracts;34:S53.

Reference Type: BACKGROUND

Other Identifiers

T6004-201/Version 2

Identifier Type: -

Identifier Source: org_study_id