Aralast alpha1-proteinase Inhibitor Surveillance Study

Phase 4

Terminated

Conditions: Alpha1-antitrypsin Deficiency

Registration Number: NCT00313144

Lead Sponsor: Baxalta now part of Shire

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 127

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
HRQoL 'Physical Functioning (PF)' From Baseline to ≤6 Months	Screening 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.
HRQoL 'Role Limitation Due to Physical Health (RP)' From Baseline to ≤6 Months	Screening 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.
HRQoL 'Bodily Pain (BP)' From Baseline to ≤6 Months	Screening 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.
HRQoL 'General Health (GH)' From Baseline to ≤6 Months	Screening 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.
HRQoL 'Vitality (VT)' From Baseline to ≤6 Months	Screening 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.
HRQoL 'Social Functioning (SF)' From Baseline to ≤6 Months	Screening 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.
HRQoL 'Role Limitation Due to Emotional Problems (RE)' From Baseline to ≤6 Months	Screening 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.
HRQoL 'Mental Health (MH)' From Baseline to ≤6 Months	Screening 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.
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	Baseline 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.
HRQoL 'Physical Component Score (PCS)' From Baseline to ≤6 Months	Screening 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.
HRQoL 'Mental Component Score (MCS)' From Baseline to ≤6 Months	Screening 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.
HRQoL For: PF, RP, BP, GH, VT, SF, RE, MH, PCS, and MCS: Baseline, Baseline to ≤6 Months, and >6 Months to ≤12 Months	Baseline 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.
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	Baseline 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.

Secondary Outcome Measures

Name	Time	Method
Healthcare Resource Utilization (HCRU) 'Frequency of Emergency Room (ER) Visits'	Baseline to 24 Months	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)
Healthcare Resource Utilization (HCRU) 'Mean Number of Emergency Room (ER) Visits'	One year prior to baseline to 24 months post-baseline	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)
Healthcare Resource Utilization (HCRU) 'Mean Length of Stay (LOS) in Hospital'	Baseline to 24 months	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)
Healthcare Resource Utilization (HCRU) 'Number of Participants Receiving Steroid Pulse Courses'	One year prior to baseline to 24 months post-baseline	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)
Healthcare Resource Utilization (HCRU) 'Number of Steroid Pulse Courses'	One year prior to baseline to 24 months post-baseline	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)
Hepatic Chemistry Parameters: Change From Baseline/Screening	Baseline to 24 months	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)
Renal and Hepatic Chemistry Parameters: Change From Baseline/Screening	Baseline to 24 months	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)
ARALAST Antibody Titers: Participants With at Least 2-Dilution Step Increases From Screening	Baseline to 24 Months	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
Healthcare Resource Utilization (HCRU) 'Frequency of Hospitalizations'	Baseline to 24 Months	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)
Healthcare Resource Utilization (HCRU) 'Number of Participants Taking Antibiotics'	One year prior to baseline to 24 months post-baseline	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)
Healthcare Resource Utilization (HCRU) 'Number of Antibiotic Courses'	One year prior to baseline to 24 months post-baseline	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)