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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT00396006
Ethics application status
Date submitted
3/11/2006
Date registered
6/11/2006
Date last updated
13/05/2021

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
Treatment: Other - Alpha1-Proteinase Inhibitor

Treatment: Other: Alpha1-Proteinase Inhibitor
60 mg/kg, weekly, intravenous infusion
Intervention code [1] 0 0
Treatment: Other
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
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
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
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
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
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
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
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
Sex
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
27/10/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/12/2007
Sample size
Target
Accrual to date
Final
21
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/study/NCT00396006
Trial related presentations / publications
Li Z, Franke RM, Morris DN, Yel L. Pharmacokinetics and Biochemical Efficacy of an alpha1-Proteinase Inhibitor (Aralast NP) in alpha1-Antitrypsin Deficiency: a Cross-Product Retrospective Comparability Analysis. Pulm Ther. 2022 Sep;8(3):311-326. doi: 10.1007/s41030-022-00199-4. Epub 2022 Aug 24.
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Takeda
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00396006