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

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Brief Title

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

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)

Brief Summary

      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.
    


Study Phase

Phase 4

Study Type

Interventional


Primary Outcome

Change in Bronchoalveolar Lavage (BAL) Epithelial Lining Fluid (ELF) Alpha1-Proteinase Inhibitor (α1-PI) Level

Secondary Outcome

 Ratio of Post- to Pre-treatment BAL ELF Antineutrophil Elastase Capacity (ANEC) Levels

Condition

Alpha 1-Antitrypsin Deficiency

Intervention

Alpha1-Proteinase Inhibitor


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

21

Start Date

October 2006


Primary Completion Date

December 2007

Eligibility 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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Baxter BioScience Investigator, MD, , 

Location Countries

Australia

Location Countries

Australia

Administrative Informations


NCT ID

NCT00396006

Organization ID

460502



Study Sponsor

Baxalta now part of Shire


Study Sponsor

Baxter BioScience Investigator, MD, Study Director, Baxter Healthcare Corporation


Verification Date

March 2011