Trial Outcomes & Findings for Efficacy and Safety Study of Augmentation Therapy With ARALAST Fraction IV-1 (Human Alpha 1 - Proteinase Inhibitor) (NCT NCT00396006)
NCT ID: NCT00396006
Last Updated: 2021-05-13
Results Overview
Median change BAL ELF antigenic α1-PI level the from baseline to post-treatment
COMPLETED
PHASE4
21 participants
BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks)
2021-05-13
Participant Flow
Participants were recruited at 5 hospital sites in New Zealand and Australia. The period studied was 1 year and 2 months.
21 participants enrolled: 4 were screen failures (i.e., did not meet inclusion/exclusion criteria), 3 were discontinued due to unevaluable baseline bronchoalveolar lavage (BAL) samples, and 1 subject withdrew consent prior to receiving investigational product.
Participant milestones
| Measure |
Participants Treated With ARALAST Fraction IV-1 (Fr. IV-1)
Weekly infusions of ARALAST Fr. IV-1 were administered to participants at a dosage of 60 mg/kg
|
|---|---|
|
Overall Study
STARTED
|
13
|
|
Overall Study
COMPLETED
|
13
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Efficacy and Safety Study of Augmentation Therapy With ARALAST Fraction IV-1 (Human Alpha 1 - Proteinase Inhibitor)
Baseline characteristics by cohort
| Measure |
Participants Treated With ARALAST Fr. IV-1
n=13 Participants
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=99 Participants
|
|
Age, Continuous
|
59.6 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
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7 Participants
n=99 Participants
|
|
Region of Enrollment
Australia
|
8 Participants
n=99 Participants
|
|
Region of Enrollment
New Zealand
|
5 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks)Population: Per protocol
Median change BAL ELF antigenic α1-PI level the from baseline to post-treatment
Outcome measures
| Measure |
Per Protocol
n=10 Participants
Treated participants with no major protocol violations, evaluable pre- and post-treatment BAL procedures, and 8 consecutive weekly treatments.
|
|---|---|
|
Change in Bronchoalveolar Lavage (BAL) Epithelial Lining Fluid (ELF) Alpha1-Proteinase Inhibitor (α1-PI) Level
|
0.28 μM
Interval -0.24 to 4.9
|
PRIMARY outcome
Timeframe: During 8 consecutive weeks of treatmentPopulation: Intent to treat
Outcome measures
| Measure |
Per Protocol
n=13 Participants
Treated participants with no major protocol violations, evaluable pre- and post-treatment BAL procedures, and 8 consecutive weekly treatments.
|
|---|---|
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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
|
0 adverse events
|
PRIMARY outcome
Timeframe: During 8 consecutive weeks of treatmentNumber of decreases in the rate or discontinuations of infusion at 0.2 mL/kg/min
Outcome measures
| Measure |
Per Protocol
n=13 Participants
Treated participants with no major protocol violations, evaluable pre- and post-treatment BAL procedures, and 8 consecutive weekly treatments.
|
|---|---|
|
Number of Changes in the Rate of Infusion
|
0 infusions
|
SECONDARY outcome
Timeframe: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks)Population: Per protocol
Median ratio of post- to pre-treatment BAL ELF ANEC levels
Outcome measures
| Measure |
Per Protocol
n=2 Participants
Treated participants with no major protocol violations, evaluable pre- and post-treatment BAL procedures, and 8 consecutive weekly treatments.
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|---|---|
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Ratio of Post- to Pre-treatment BAL ELF Antineutrophil Elastase Capacity (ANEC) Levels
|
1.22 μM
Interval 0.63 to 1.81
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SECONDARY outcome
Timeframe: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks)Population: No per protocol subject had both pre- and post-treatment analytes available, therefore no analysis could be performed on this outcome measure
Median change in the ratio of BAL ELF α1-PI to HNE complex concentration from baseline to post-treatment
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Blood samples were collected at baseline and after 8 consecutive weeks of treatmentPopulation: Per protocol
Mean change in the plasma level of α1-PI from baseline to post-treatment
Outcome measures
| Measure |
Per Protocol
n=12 Participants
Treated participants with no major protocol violations, evaluable pre- and post-treatment BAL procedures, and 8 consecutive weekly treatments.
|
|---|---|
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Change in the α1-PI Plasma Level
|
10.34 μM
Standard Deviation 2.50
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SECONDARY outcome
Timeframe: Blood samples were collected at baseline and after 8 consecutive weeks of treatmentPopulation: Per protocol
Mean change in the plasma ANEC level from baseline to post-treatment
Outcome measures
| Measure |
Per Protocol
n=12 Participants
Treated participants with no major protocol violations, evaluable pre- and post-treatment BAL procedures, and 8 consecutive weekly treatments.
|
|---|---|
|
Change in the Plasma Antineutrophil Elastase Capacity (ANEC) Level
|
9.46 μM
Standard Deviation 2.31
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SECONDARY outcome
Timeframe: During 8 consecutive weeks of infusionPopulation: Intention to treat
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
Outcome measures
| Measure |
Per Protocol
n=13 Participants
Treated participants with no major protocol violations, evaluable pre- and post-treatment BAL procedures, and 8 consecutive weekly treatments.
|
|---|---|
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Clinically Significant Changes in Vital Signs From Pre- to Post-Infusion
|
2 # Clinically significant events
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OTHER_PRE_SPECIFIED outcome
Timeframe: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks)Population: Per protocol population with both pre- and post-treatment analytes available from BAL procedures
Median change in the BAL ELF Free Neutrophil Elastase Level from baseline to post-treatment
Outcome measures
| Measure |
Per Protocol
n=3 Participants
Treated participants with no major protocol violations, evaluable pre- and post-treatment BAL procedures, and 8 consecutive weekly treatments.
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|---|---|
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Change in the BAL ELF Free Neutrophil Elastase Level
|
41.17 nM
Interval 3.91 to 41.61
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OTHER_PRE_SPECIFIED outcome
Timeframe: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks)Population: Per protocol
Median ratio of post- to pre-treatment BAL ELF Total Neutrophil Elastase Level
Outcome measures
| Measure |
Per Protocol
n=5 Participants
Treated participants with no major protocol violations, evaluable pre- and post-treatment BAL procedures, and 8 consecutive weekly treatments.
|
|---|---|
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Ratio of Post- to Pre-treatment BAL ELF Total Neutrophil Elastase Level
|
1.24 nM
Interval 0.47 to 30.97
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OTHER_PRE_SPECIFIED outcome
Timeframe: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks)Population: Per protocol
Median ratio of post- to pre-treatment BAL ELF IL-8 Level
Outcome measures
| Measure |
Per Protocol
n=6 Participants
Treated participants with no major protocol violations, evaluable pre- and post-treatment BAL procedures, and 8 consecutive weekly treatments.
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|---|---|
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Ratio of Post- to Pre-treatment BAL ELF Interleukin 8 (IL-8) Level
|
1.46 pg/mL
Interval 0.48 to 10.38
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OTHER_PRE_SPECIFIED outcome
Timeframe: BAL procedures were performed at baseline and after 8 consecutive weeks of treatment (minimum of 12 weeks)Population: Per protocol population with both pre- and post-treatment analytes available from BAL procedures
Median change in the BAL ELF TNF-α from baseline to post-treatment
Outcome measures
Outcome data not reported
Adverse Events
Intent to Treat
Serious adverse events
| Measure |
Intent to Treat
n=13 participants at risk
Treated participants with relevant assessments, e.g. if pre- and post-treatment BAL procedures were required to assess the parameter, then the participant had both evaluable BAL procedures.
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|---|---|
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Investigations
Hepatitis A antibody positive
|
7.7%
1/13 • Number of events 1 • 1 year, 2 months
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Other adverse events
| Measure |
Intent to Treat
n=13 participants at risk
Treated participants with relevant assessments, e.g. if pre- and post-treatment BAL procedures were required to assess the parameter, then the participant had both evaluable BAL procedures.
|
|---|---|
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General disorders
Inflammation
|
7.7%
1/13 • Number of events 1 • 1 year, 2 months
|
|
General disorders
Sluggishness
|
15.4%
2/13 • Number of events 2 • 1 year, 2 months
|
|
General disorders
Vessel puncture site haematoma
|
7.7%
1/13 • Number of events 1 • 1 year, 2 months
|
|
Infections and infestations
Bronchitis
|
7.7%
1/13 • Number of events 1 • 1 year, 2 months
|
|
Infections and infestations
Sinusitis
|
7.7%
1/13 • Number of events 1 • 1 year, 2 months
|
|
Injury, poisoning and procedural complications
Contusion
|
7.7%
1/13 • Number of events 1 • 1 year, 2 months
|
|
Injury, poisoning and procedural complications
Post procedural complication
|
15.4%
2/13 • Number of events 3 • 1 year, 2 months
|
|
Investigations
Blood pressure systolic abnormal
|
7.7%
1/13 • Number of events 1 • 1 year, 2 months
|
|
Investigations
Respiratory rate increased
|
7.7%
1/13 • Number of events 1 • 1 year, 2 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.7%
1/13 • Number of events 1 • 1 year, 2 months
|
|
Nervous system disorders
Migrane
|
7.7%
1/13 • Number of events 1 • 1 year, 2 months
|
|
Respiratory, thoracic and mediastinal disorders
Chest discomfort
|
7.7%
1/13 • Number of events 1 • 1 year, 2 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
7.7%
1/13 • Number of events 6 • 1 year, 2 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The data from the study shall be published (if applicable) by the sponsor. The investigators and the steering committee may be involved if agreed to by the sponsor. Neither the investigator nor any other person within his/her institution has the right to publish separately or individually without permission by the sponsor.
- Publication restrictions are in place
Restriction type: OTHER