Efficacy and Safety Study of Augmentation Therapy With ARALAST Fraction IV-1 (Human Alpha 1 - Proteinase Inhibitor)

This study has been completed.
Sponsor:
Information provided by:
Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:
NCT00396006
First received: November 3, 2006
Last updated: March 3, 2011
Last verified: March 2011
  Purpose

The purpose of this study is to evaluate the effects of weekly augmentation therapy with ARALAST Fraction IV-1 (Fr IV-1) on epithelial lining fluid (ELF) alpha 1-proteinase inhibitor levels and other ELF analytes and to assess the safety of the treatment. Eligible subjects with a diagnosis of severe congenital alpha 1-antitrypsin deficiency will receive 8 consecutive weekly treatments with 60 mg/kg/week of functional ARALAST Fr IV-1 administered intravenously. The efficacy and safety assessments will include two bronchoscopies with bronchoalveolar lavage on study initiation and on study termination and multiple imaging and laboratory safety assessments. Each subject will participate for a minimum of 12 weeks.


Condition Intervention Phase
Alpha 1-Antitrypsin Deficiency
Biological: Alpha1-Proteinase Inhibitor
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effect of Augmentation Therapy With ARALAST Fraction IV-1 (ARALAST) Alpha1-Proteinase Inhibitor (α1-PI) on the Level of α1-PI and Other Analytes in the Bronchoalveolar (BAL) Epithelial Lining Fluid (ELF)

Resource links provided by NLM:


Further study details as provided by Baxter Healthcare Corporation:

Primary Outcome Measures:
  • Change in Bronchoalveolar Lavage (BAL) Epithelial Lining Fluid (ELF) Alpha1-Proteinase Inhibitor (α1-PI) Level [ Time Frame: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks) ] [ Designated as safety issue: No ]
    Median change BAL ELF antigenic α1-PI level the from baseline to post-treatment

  • The Number of Adverse Events (AEs) Related to the Infusion of ARALAST Fr. IV 1 Administered at a Rate of 0.2 mL/kg/Min [ Time Frame: During 8 consecutive weeks of treatment ] [ Designated as safety issue: Yes ]
  • Number of Changes in the Rate of Infusion [ Time Frame: During 8 consecutive weeks of treatment ] [ Designated as safety issue: Yes ]
    Number of decreases in the rate or discontinuations of infusion at 0.2 mL/kg/min


Secondary Outcome Measures:
  • Ratio of Post- to Pre-treatment BAL ELF Antineutrophil Elastase Capacity (ANEC) Levels [ Time Frame: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks) ] [ Designated as safety issue: No ]
    Median ratio of post- to pre-treatment BAL ELF ANEC levels

  • Change in in the Ratio of BAL ELF α1-PI to Human Neutrophil Elastase (HNE) Complex Concentration [ Time Frame: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks) ] [ Designated as safety issue: No ]
    Median change in the ratio of BAL ELF α1-PI to HNE complex concentration from baseline to post-treatment

  • Change in the α1-PI Plasma Level [ Time Frame: Blood samples were collected at baseline and after 8 consecutive weeks of treatment ] [ Designated as safety issue: No ]
    Mean change in the plasma level of α1-PI from baseline to post-treatment

  • Change in the Plasma Antineutrophil Elastase Capacity (ANEC) Level [ Time Frame: Blood samples were collected at baseline and after 8 consecutive weeks of treatment ] [ Designated as safety issue: No ]
    Mean change in the plasma ANEC level from baseline to post-treatment

  • Clinically Significant Changes in Vital Signs From Pre- to Post-Infusion [ Time Frame: During 8 consecutive weeks of infusion ] [ Designated as safety issue: Yes ]

    Clinically significant changes in vital signs from pre- to post-infusion are:

    • Heart rate: 25% increase above pre-infusion value
    • Blood pressure: ≥ 30 mm Hg change from pre-infusion blood pressure (systolic or diastolic)
    • Temperature: an increase in body temperature to >38°C (>100.4°F). If the pre-infusion body temperature was already >38°C (>100.4°F), then any further increase in body temperature by 1.1°C (1.98°F) or more was considered clinically significant.
    • Respiratory rate: 25% increase above pre-infusion value


Enrollment: 21
Study Start Date: October 2006
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: Alpha1-Proteinase Inhibitor
    60 mg/kg, weekly, intravenous infusion
    Other Names:
    • ARALAST Fr.IV-1
    • ARALAST NP
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed and dated informed consent.
  • Male or female 18 years of age or older.
  • Documented, endogenous serum α1-PI level < 40 mg/dL measured at screening (unless otherwise approved by the Sponsor) after a minimum of 28-day washout of any prior replacement therapy (if applicable).
  • Phenotype Pi Z (which includes Pi*Z/Z, Pi*Z/Null, or Pi*Malton/Z), or Pi*Null/Null.
  • Pulmonary functions at screening meeting the following criteria:

    1. Forced expiratory volume at 1 second (FEV1) >= 50% of predicted value; or
    2. FEV1 > 35% of predicted value and diffusing capacity for carbon monoxide > 45% of predicated value, with no supplemental oxygen therapy and < 3 pulmonary exacerbations or bronchitis requiring antibiotics/corticosteroids within the past 12 months).
  • For any female of childbearing potential, a negative urine test for pregnancy within 7 days prior to the first bronchoalveolar lavage (BAL) visit and agreement to employ adequate birth control measures for the duration of the study.
  • No clinically significant abnormalities detected on a 12-lead electrocardiogram (ECG) performed at the screening visit (ECG previously obtained within the past 12 months may be used, if available).
  • Laboratory results obtained at the screening visit, meeting the following criteria:

    1. Serum alanine aminotransferase (ALT) <= 2 times upper limit of normal (ULN)
    2. Serum aspartate aminotransferase (AST) <= 2 times ULN
    3. Serum total bilirubin <= 2 times ULN
    4. Proteinuria < +2 on dipstick analysis
    5. Serum creatinine <= 1.5 times ULN
    6. Absolute neutrophil count (ANC) >= 1500 cells/mm3
    7. Hemoglobin (Hgb) >= 10.0 g/dL
    8. Platelet count >= 105/mm3
  • If the subject is treated with respiratory medications, such as inhaled bronchodilators or inhaled corticosteroids, or other chronic medications for the treatment of the subjects´s other medical condition(s), the subject's medication doses were unchanged for at least 14 days prior to the baseline BAL visit.

Exclusion Criteria:

  • Clinically significant pulmonary impairment, other than chronic pulmonary disease (COPD).
  • The subject has received any alpha 1 proteinase inhibitor (α1-PI) augmentation therapy (e.g., Prolastin, Zemaira, Aralast, or an investigational α1-PI, by any route including intravenous and inhaled) within 28 days prior to screening.
  • The subject has received an investigational drug or device within 1 month prior to screening, or the subject is currently receiving an investigational drug or device. If the subject receives another investigational drug or device after enrollment, the subjects is to be withdrawn from the trial.
  • Presence of clinical symptoms of any lower respiratory tract infection or acute pulmonary exacerbation within 14 days prior to screening.
  • The subject has a known selective Immunoglobulin A (IgA) deficiency (IgA level less than 15 mg/dL) and/or antibody against IgA.
  • The subject is pregnant or lactating, or intends to become pregnant during the course of the study.
  • The subject is not a suitable candidate for a BAL procedure.
  • Moderate or severe bronchiectasis (total daily sputum production > 10 mL).
  • Clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject safety or compliance.
  • Prior history of adverse reaction to local anaesthetics, sedatives, pain control drugs, and other medication employed at the study center for perioperative care associated with the BAL procedure.
  • Long-term use of oral or parenteral glucocorticosteroid within 28 days prior to screening.
  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: NCT00396006

Locations
Australia, South Australia
Adelaide, South Australia, Australia
Australia, Victoria
Melbourne, Victoria, Australia
Australia, Western Australia
Nedlands, Western Australia, Australia
New Zealand
Otahuhu, Auckland, New Zealand
Hamilton, New Zealand
Sponsors and Collaborators
Baxter Healthcare Corporation
Investigators
Study Director: Baxter BioScience Investigator, MD Baxter Healthcare Corporation
  More Information

No publications provided

Responsible Party: David Gelmont, MD Global Medical Director, Head of Specialty Products TA, BioTherapeutics, Baxter Healthcare Corporation
ClinicalTrials.gov Identifier: NCT00396006     History of Changes
Other Study ID Numbers: 460502
Study First Received: November 3, 2006
Results First Received: December 15, 2010
Last Updated: March 3, 2011
Health Authority: United States: Food and Drug Administration

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
Alpha 1-Antitrypsin
Protease Inhibitors
Trypsin Inhibitors
Serine Proteinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 25, 2014