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

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Brief Title

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

Official Title

A Randomized Double-blind Crossover Study to Assess the Safety and Pharmacokinetics of Two Different Doses of Weekly Intravenous Administration of Alpha1-Proteinase Inhibitor (Human) Prolastin®-C in Subjects With Alpha1-Antitrypsin Deficiency

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Subjects With Treatment-Emergent Adverse Events (TEAEs)

Secondary Outcome

 AUC0-7days

Condition

Emphysema

Intervention

Prolastin-C, 60 mg/kg

Study Arms / Comparison Groups

 Prolastin-C, 60 mg/kg
Description:  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).

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

30

Start Date

November 2010

Completion Date

January 2012

Primary Completion Date

January 2012

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
      

Gender

All

Ages

18 Years - 70 Years

Accepts Healthy Volunteers

No

Contacts

Mark Brantly, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01213043

Organization ID

T6004-201/Version 2


Responsible Party

Sponsor

Study Sponsor

Grifols Therapeutics LLC


Study Sponsor

Mark Brantly, MD, Principal Investigator, University of Florida


Verification Date

April 2013