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

November 3, 2006
March 3, 2011
October 2006
December 2007   (final data collection date for primary outcome measure)
  • 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
Not Provided
Complete list of historical versions of study NCT00396006 on ClinicalTrials.gov Archive Site
  • 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
Not Provided
Not Provided
Not Provided
 
Efficacy and Safety Study of Augmentation Therapy With ARALAST Fraction IV-1 (Human Alpha 1 - Proteinase Inhibitor)
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)

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.

Not Provided
Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Alpha 1-Antitrypsin Deficiency
Biological: Alpha1-Proteinase Inhibitor
60 mg/kg, weekly, intravenous infusion
Other Names:
  • ARALAST Fr.IV-1
  • ARALAST NP
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
21
Not Provided
December 2007   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Australia,   New Zealand
 
NCT00396006
460502
Not Provided
David Gelmont, MD Global Medical Director, Head of Specialty Products TA, BioTherapeutics, Baxter Healthcare Corporation
Baxter Healthcare Corporation
Not Provided
Study Director: Baxter BioScience Investigator, MD Baxter Healthcare Corporation
Baxter Healthcare Corporation
March 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP