Aralast alpha1-proteinase Inhibitor Surveillance Study

Study Overview
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Brief Summary
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The primary objectives of this Phase 4, open label, prospective U.S. surveillance study are to evaluate the health outcomes of Alpha 1-Antitrypsin (AAT)-deficient subjects who are initiating treatment with ARALAST on patient-related outcomes (PRO), i.e., health-related quality of life (HRQoL), healthcare resource utilization (HCRU), and various laboratory analyses to evaluate the safety of long-term administration of ARALAST. Up to 120 subjects will be enrolled and assessed for HRQoL and HCRU at baseline and every 6-months thereafter, for 2 years. A subset of subjects will be enrolled into the blood draw portion of the study, which will also include assessments of antibodies to ARALAST, and chemistry panel. Subjects will be treated according to the prescribing (attending) physician's instructions based on the prescribing information given in the ARALAST package insert.

Official Title
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ARALAST alpha1-proteinase Inhibitor (α1-PI) Surveillance Study

Conditions
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Alpha1-antitrypsin Deficiency

Intervention / Treatment
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* Drug: ARALAST Alpha1-Proteinase Inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 18 years of age or older Diagnosis of AAT deficiency associated emphysema Active prescription for augmentation therapy with ARALAST On service with Coram (a speciality pharmacy provider) Signed and dated informed consent Exclusion Criteria: Clinically significant medical (other than COPD), psychiatric, or cognitive illness that, in the opinion of Coram or the sponsor or the investigator, may compromise subject safety or compliance (such as end stage renal or hepatic or heart disease, or metastatic cancer or any difficulty in communicating over the telephone lines) Previous treatment with ARALAST (i.e. subjects who had previously received and then discontinued ARALAST augmentation therapy and are now restarting ARALAST will be excluded from the study)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: ARALAST Alpha1-Proteinase Inhibitor|Weekly ARALAST infusions for 2 years, dose and mode of administration as prescribed by the physician|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HRQoL 'Physical Functioning (PF)' From Baseline to ≤6 Months | Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The data transformation process was based on: Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000. | Screening to ≤ 6 Months | 
| HRQoL 'Role Limitation Due to Physical Health (RP)' From Baseline to ≤6 Months | Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The data transformation process was based on Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000. | Screening to ≤ 6 Months | 
| HRQoL 'Bodily Pain (BP)' From Baseline to ≤6 Months | Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The data transformation process was based on Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000. | Screening to ≤ 6 Months | 
| HRQoL 'General Health (GH)' From Baseline to ≤6 Months | Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The data transformation process was based on Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000. | Screening to ≤ 6 Months | 
| HRQoL 'Vitality (VT)' From Baseline to ≤6 Months | Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The data transformation process was based on Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000. | Screening to ≤ 6 Months | 
| HRQoL 'Social Functioning (SF)' From Baseline to ≤6 Months | Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The data transformation process was based on Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000. | Screening to ≤ 6 Months | 
| HRQoL 'Role Limitation Due to Emotional Problems (RE)' From Baseline to ≤6 Months | Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The data transformation process was based on Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000. | Screening to ≤ 6 Months | 
| HRQoL 'Mental Health (MH)' From Baseline to ≤6 Months | Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The data transformation process was based on Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000. | Screening to ≤ 6 Months | 
| HRQoL 'Physical Component Score (PCS)' From Baseline to ≤6 Months | SF-36 scores for baseline (screening) versus the period from baseline to ≤6 Months. The PCS is a summary scale of the dimensions physical functioning, role physical, bodily pain, and general health. The component score is normalized to a standard population. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. | Screening to ≤ 6 Months | 
| HRQoL 'Mental Component Score (MCS)' From Baseline to ≤6 Months | SF-36 scores for baseline (screening) versus the period from baseline to ≤6 Months. The MCS is a summary scale of the dimensions vitality, social functioning, role emotional, and mental health Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. | Screening to ≤ 6 Months | 
| HRQoL For: PF, RP, BP, GH, VT, SF, RE, MH, PCS, and MCS: Baseline, Baseline to ≤6 Months, and >6 Months to ≤12 Months | SF-36 Scores- baseline thru 12 months, where data was available. Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The Data transformation process was based on: Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000. | Baseline to 12 months | 
| HRQoL for PF, RP, BP, GH, VT, SF, RE, MH, PCS, and MCS Scores: Baseline, Baseline to ≤6 Months, >6 Months to ≤12 Months, and >12 Months to ≤18 Months | SF-36 Scores- baseline thru 12 months, where data was available. Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The Data transformation process was based on: Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000. | Baseline to 12 months | 
| HRQoL for PF, RP, BP, GH, VT, SF, RE, MH, PCS, and MCS Scores: Baseline, Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months | SF-36 Scores- baseline thru 24 months, where data was available. Change in quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores. The Data transformation process was based on: Ware et al. How to Score Version 2 of the SF-36® Health Survey. Lincoln, RI: Quality Metric Incorporated; 2000. | Baseline to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Healthcare Resource Utilization (HCRU) 'Frequency of Emergency Room (ER) Visits' | Number of participants with indicated number of ER visits (0, 1, 2, 3, ≥4 ER visits per participant) during each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months) | Baseline to 24 Months | 
| Healthcare Resource Utilization (HCRU) 'Mean Number of Emergency Room (ER) Visits' | Mean number of ER visits one year prior to baseline/screening, and during each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months) | One year prior to baseline to 24 months post-baseline | 
| Healthcare Resource Utilization (HCRU) 'Frequency of Hospitalizations' | Number of participants with indicated number of hospitalizations during each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months) | Baseline to 24 Months | 
| Healthcare Resource Utilization (HCRU) 'Mean Length of Stay (LOS) in Hospital' | Mean LOS during each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months) | Baseline to 24 months | 
| Healthcare Resource Utilization (HCRU) 'Number of Participants Taking Antibiotics' | Number of participants taking antibiotics one year prior to baseline/screening, and during each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months) | One year prior to baseline to 24 months post-baseline | 
| Healthcare Resource Utilization (HCRU) 'Number of Antibiotic Courses' | Number of antibiotic courses (i.e. number of antibiotic prescriptions) one year prior to baseline/screening, and during each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months) | One year prior to baseline to 24 months post-baseline | 
| Healthcare Resource Utilization (HCRU) 'Number of Participants Receiving Steroid Pulse Courses' | Number of participants receiving steroid pulse courses (i.e. number of steroid prescriptions) one year prior to baseline/screening, and during each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months) | One year prior to baseline to 24 months post-baseline | 
| Healthcare Resource Utilization (HCRU) 'Number of Steroid Pulse Courses' | Number of steroid pulse courses (i.e. number of steroid prescriptions) one year prior to baseline/screening, and during each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months) | One year prior to baseline to 24 months post-baseline | 
| Hepatic Chemistry Parameters: Change From Baseline/Screening | Summary of changes in hepatic (total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase) parameters from screening/baseline through each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months) | Baseline to 24 months | 
| Renal and Hepatic Chemistry Parameters: Change From Baseline/Screening | Summary of changes in hepatic (total bilirubin) and renal (Blood urea nitrogen (BUN), creatinine) parameters from screening/baseline through each window period (Baseline to ≤6 Months, >6 Months to ≤12 Months, >12 Months to ≤18 Months, and >18 Months to ≤24 Months) | Baseline to 24 months | 
| ARALAST Antibody Titers: Participants With at Least 2-Dilution Step Increases From Screening | All IgG and IgM titers at screening were ≤ 4. A 2-dilution step increase was defined as follows: • The titer at each 6-month visit must be ≥ 4 when the screening titer = 0 • Each 6-month visit titer / screening titer should be ≥ 4. 6 month window periods are: baseline to ≤6 months, >6 months to ≤12 months, >12 months to ≤18 months, and >18 months to ≤24 months | Baseline to 24 Months |