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

April 8, 2013 updated by: Grifols Therapeutics LLC

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

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).

Study Overview

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 Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Florida
      • Gainesville, Florida, United States, 32610-0225
        • University of Florida College of Medicine
      • Miami, Florida, United States, 33136
        • University of Miami
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University Hosptial/Temple Lung Center
    • South Carolina
      • Charleston, South Carolina, United States, 29425-6300
        • Medical University of South Carolina, Division of Pulmonary and Critical Care Medicine
    • Texas
      • Tyler, Texas, United States, 75708
        • The University of Texas Health Science Center at Tyler

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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).
60 mg/kg weekly infusion of Prolastin-C for 8 weeks
Other Names:
  • Alpha1-Proteinase Inhibitor
  • Alpha1-Proteinase Inhibitor (Human), Modified Process
  • Alpha-1 MP
Experimental: 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).
120 mg/kg weekly infusion of Prolastin-C for 8 weeks
Other Names:
  • Alpha1-Proteinase Inhibitor
  • Alpha1-Proteinase Inhibitor (Human), Modified Process
  • Alpha-1 MP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Subjects With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: 22 weeks
Number of subjects experiencing at least one TEAE. TEAEs were defined as any adverse event (AE) during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).
22 weeks
Subjects With Drug-Related TEAE(s)
Time Frame: 22 weeks
Number of subjects with at least one TEAE that was determined by the Investigator to be either "possibly related" or "related" to the investigational product (i.e., Prolastin-C).
22 weeks
Subjects With Treatment-Emergent Serious Adverse Events (SAEs)
Time Frame: 22 weeks
Number of subjects who experienced at least one treatment-emergent SAE.
22 weeks
Subjects Withdrawn Due to an AE(s)
Time Frame: 22 weeks
Number of subjects who were withdrawn from the study due to at least one AE.
22 weeks
Subjects With Treatment-Emergent Pulmonary Exacerbation(s)
Time Frame: 22 weeks
Number of subjects with at least one treatment-emergent pulmonary exacerbation
22 weeks
Subjects With Severe TEAE(s) or Pulmonary Exacerbation(s)
Time Frame: 22 weeks
Number of subjects who experienced at least one severe TEAE or pulmonary exacerbation.
22 weeks
Number of TEAEs
Time Frame: 22 Weeks
Total number of TEAEs reported.
22 Weeks
Number of Drug-related TEAEs
Time Frame: 22 Weeks
Total number of drug-related TEAEs reported
22 Weeks
Number of Treatment-Emergent Pulmonary Exacerbations
Time Frame: 22 Weeks
Total number of treatment-emergent pulmonary exacerbations.
22 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AUC0-7days
Time Frame: Week 8 and Week 18 at the following timepoints: 0 (pre-infusion), completion of first infusion bag, completion of 2nd infusion bag, and 15 min, 30 min, and 1, 2, 4, 8, 24, 48, 120, and 168 hours post-dose
Area Under the Alpha-1 PI Concentration-Time Curve from Day 0 to Day 7
Week 8 and Week 18 at the following timepoints: 0 (pre-infusion), completion of first infusion bag, completion of 2nd infusion bag, and 15 min, 30 min, and 1, 2, 4, 8, 24, 48, 120, and 168 hours post-dose
Mean Trough
Time Frame: Single measurment immediately prior to infusion at Weeks 6, 7, 8, 9 and Weeks 16, 17, 18, 19
The average trough concentration at steady-state, calculated as the mean value using the four Trough measurements obtained at Weeks 6, 7, 8 and at 7 days (168 hours) post infusion at Week 8 for the first treatment period or prior to the start of the infusions at Weeks 16, 17, 18, and at 7 days (168 hours) post infusion at Week 18 for the second treatment period.
Single measurment immediately prior to infusion at Weeks 6, 7, 8, 9 and Weeks 16, 17, 18, 19

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Michael Campos, MD, University of Miami
  • Principal Investigator: Friedrich Kueppers, MD, Temple University Hospital/Temple Lung Center
  • Principal Investigator: James Stocks, MD, The University of Texas Health Science Center at Tyler
  • Principal Investigator: Charlie Strange, MD, Medical University of South Carolina, Division of Pulmonary and Critical Care Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • 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.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2010

Primary Completion (Actual)

January 1, 2012

Study Completion (Actual)

January 1, 2012

Study Registration Dates

First Submitted

September 29, 2010

First Submitted That Met QC Criteria

September 29, 2010

First Posted (Estimate)

October 1, 2010

Study Record Updates

Last Update Posted (Estimate)

May 20, 2013

Last Update Submitted That Met QC Criteria

April 8, 2013

Last Verified

April 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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