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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier:
NCT01213043
First received: September 29, 2010
Last updated: April 8, 2013
Last verified: April 2013
  Purpose

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).


Condition Intervention Phase
Emphysema
Alpha 1-antitrypsin Deficiency (AATD)
Biological: Prolastin-C, 60 mg/kg
Biological: Prolastin-C, 120 mg/kg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Grifols Therapeutics Inc.:

Primary Outcome Measures:
  • Subjects With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: 22 weeks ] [ Designated as safety issue: Yes ]
    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).

  • Subjects With Drug-Related TEAE(s) [ Time Frame: 22 weeks ] [ Designated as safety issue: Yes ]
    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).

  • Subjects With Treatment-Emergent Serious Adverse Events (SAEs) [ Time Frame: 22 weeks ] [ Designated as safety issue: Yes ]
    Number of subjects who experienced at least one treatment-emergent SAE.

  • Subjects Withdrawn Due to an AE(s) [ Time Frame: 22 weeks ] [ Designated as safety issue: Yes ]
    Number of subjects who were withdrawn from the study due to at least one AE.

  • Subjects With Treatment-Emergent Pulmonary Exacerbation(s) [ Time Frame: 22 weeks ] [ Designated as safety issue: Yes ]
    Number of subjects with at least one treatment-emergent pulmonary exacerbation

  • Subjects With Severe TEAE(s) or Pulmonary Exacerbation(s) [ Time Frame: 22 weeks ] [ Designated as safety issue: Yes ]
    Number of subjects who experienced at least one severe TEAE or pulmonary exacerbation.

  • Number of TEAEs [ Time Frame: 22 Weeks ] [ Designated as safety issue: Yes ]
    Total number of TEAEs reported.

  • Number of Drug-related TEAEs [ Time Frame: 22 Weeks ] [ Designated as safety issue: Yes ]
    Total number of drug-related TEAEs reported

  • Number of Treatment-Emergent Pulmonary Exacerbations [ Time Frame: 22 Weeks ] [ Designated as safety issue: Yes ]
    Total number of treatment-emergent pulmonary exacerbations.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Area Under the Alpha-1 PI Concentration-Time Curve from Day 0 to Day 7

  • Mean Trough [ Time Frame: Single measurment immediately prior to infusion at Weeks 6, 7, 8, 9 and Weeks 16, 17, 18, 19 ] [ Designated as safety issue: No ]
    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.


Enrollment: 30
Study Start Date: November 2010
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
Biological: Prolastin-C, 60 mg/kg
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).
Biological: Prolastin-C, 120 mg/kg
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01213043

Locations
United States, Florida
University of Florida College of Medicine
Gainesville, Florida, United States, 32610-0225
University of Miami
Miami, Florida, United States, 33136
United States, Pennsylvania
Temple University Hosptial/Temple Lung Center
Philadelphia, Pennsylvania, United States, 19140
United States, South Carolina
Medical University of South Carolina, Division of Pulmonary and Critical Care Medicine
Charleston, South Carolina, United States, 29425-6300
United States, Texas
The University of Texas Health Science Center at Tyler
Tyler, Texas, United States, 75708
Sponsors and Collaborators
Grifols Therapeutics Inc.
Investigators
Principal Investigator: Mark Brantly, MD University of Florida
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
  More Information

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.

Responsible Party: Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT01213043     History of Changes
Other Study ID Numbers: T6004-201/Version 2
Study First Received: September 29, 2010
Results First Received: February 26, 2013
Last Updated: April 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Grifols Therapeutics Inc.:
emphysema
alpha 1-antitrypsin
alpha 1-antitrypsin deficiency (AATD)
alpha 1-proteinase inhibitor (Alpha-1 PI)

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

ClinicalTrials.gov processed this record on September 18, 2014