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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00396006




Registration number
NCT00396006
Ethics application status
Date submitted
3/11/2006
Date registered
6/11/2006
Date last updated
24/11/2017

Titles & IDs
Public title
Efficacy and Safety Study of Augmentation Therapy With ARALAST Fraction IV-1 (Human Alpha 1 - Proteinase Inhibitor)
Scientific title
The Effect of Augmentation Therapy With ARALAST Fraction IV-1 (ARALAST) Alpha1-Proteinase Inhibitor (a1-PI) on the Level of a1-PI and Other Analytes in the Bronchoalveolar (BAL) Epithelial Lining Fluid (ELF)
Secondary ID [1] 0 0
460502
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alpha 1-Antitrypsin Deficiency 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Alpha1-Proteinase Inhibitor

Other interventions: Alpha1-Proteinase Inhibitor
60 mg/kg, weekly, intravenous infusion

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in Bronchoalveolar Lavage (BAL) Epithelial Lining Fluid (ELF) Alpha1-Proteinase Inhibitor (a1-PI) Level - Median change BAL ELF antigenic a1-PI level the from baseline to post-treatment
Timepoint [1] 0 0
BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks)
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
During 8 consecutive weeks of treatment
Primary outcome [3] 0 0
Number of Changes in the Rate of Infusion - Number of decreases in the rate or discontinuations of infusion at 0.2 mL/kg/min
Timepoint [3] 0 0
During 8 consecutive weeks of treatment
Secondary outcome [1] 0 0
Ratio of Post- to Pre-treatment BAL ELF Antineutrophil Elastase Capacity (ANEC) Levels - Median ratio of post- to pre-treatment BAL ELF ANEC levels
Timepoint [1] 0 0
BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks)
Secondary outcome [2] 0 0
Change in in the Ratio of BAL ELF a1-PI to Human Neutrophil Elastase (HNE) Complex Concentration - Median change in the ratio of BAL ELF a1-PI to HNE complex concentration from baseline to post-treatment
Timepoint [2] 0 0
BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks)
Secondary outcome [3] 0 0
Change in the a1-PI Plasma Level - Mean change in the plasma level of a1-PI from baseline to post-treatment
Timepoint [3] 0 0
Blood samples were collected at baseline and after 8 consecutive weeks of treatment
Secondary outcome [4] 0 0
Change in the Plasma Antineutrophil Elastase Capacity (ANEC) Level - Mean change in the plasma ANEC level from baseline to post-treatment
Timepoint [4] 0 0
Blood samples were collected at baseline and after 8 consecutive weeks of treatment
Secondary outcome [5] 0 0
Clinically Significant Changes in Vital Signs From Pre- to Post-Infusion - 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
Timepoint [5] 0 0
During 8 consecutive weeks of infusion

Eligibility
Key inclusion criteria
- Signed and dated informed consent.

- Male or female 18 years of age or older.

- Documented, endogenous serum a1-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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Clinically significant pulmonary impairment, other than chronic pulmonary disease
(COPD).

- The subject has received any alpha 1 proteinase inhibitor (a1-PI) augmentation therapy
(e.g., Prolastin, Zemaira, Aralast, or an investigational a1-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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Melbourne
Recruitment hospital [3] 0 0
- Nedlands
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Hamilton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Baxalta now part of Shire
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00396006
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Baxter BioScience Investigator, MD
Address 0 0
Baxter Healthcare Corporation
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications