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Extension Study of Zemaira® i.v. Administration in Subjects With Emphysema Due to alpha1-proteinase Inhibitor Deficiency.

Primary Purpose

Emphysema, Alpha 1-proteinase Inhibitor Deficiency

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Alpha1- proteinase inhibitor [human]
Sponsored by
CSL Behring
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Emphysema focused on measuring Alpha1-proteinase inhibitor deficiency, Chronic augmentation and maintenance therapy, Emphysema, Emphysema due to Alpha 1-proteinase inhibitor deficiency

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects who have completed the 2-year treatment and observation period in the Phase 3/4 Zemaira® CE1226_4001 study (NCT00261833) and are willing to sign informed consent
  • Males, and non-pregnant, non-lactating females, whose screening pregnancy test is negative and who are using contraceptive methods deemed reliable by the investigator

Exclusion Criteria:

  • Individuals residing in the US
  • Current evidence of alcohol abuse or abuse of drugs such as barbiturates, benzodiazepines, amphetamines, cocaine, opioids, and cannabinoids
  • History of allergy, anaphylactic reaction, or severe systemic response to human plasma derived products, or known mannitol hypersensitivity, or history of prior adverse reaction to mannitol
  • Current tobacco smoker (smoking must be discontinued for at least 6 months prior to study participation)
  • Conditions or behaviors that interfere with attending scheduled study visits in the opinion of the investigator
  • History of non-compliance
  • Administration of any other experimental new drug or participation in an investigation of a marketed product
  • Inability to perform necessary study procedures

Sites / Locations

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Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Zemaira®

Arm Description

Outcomes

Primary Outcome Measures

Rate of Change of Adjusted Lung Density
As measured by centralized, standardized computer tomographic (CT) lung densitometry. CT scans were acquired at 2 inspiration states: TLC (Total Lung Capacity; ie, full inspiration) and FRC (Functional Residual Capacity; ie, full expiration). Results were adjusted for total lung volume and are presented as point estimates for the average rate of decline in the early start and delayed start subgroups from a linear random regression model with country, inspiration state (only for 'TLC and FRC state'), time (time elapsed since Day 1 [CE1226_4001]), treatment and treatment by time interaction as fixed effects and subject and subject by time interaction as random coefficients.

Secondary Outcome Measures

Absolute Change in Adjusted Lung Density
Absolute change from baseline to 2 years as measured by centralized, standardized CT lung densitometry. CT scans were acquired at 2 inspiration states: TLC (ie, full inspiration) and FRC (ie, full expiration). Results were adjusted for total lung volume and are presented as point estimates for the average absolute change in the early start and delayed start subgroups from an analysis of covariance (ANCOVA) model with country, treatment, and baseline lung density as fixed effects and inspiration state as a repeated random effect. The baseline is the last assessment from the preceding study CE1226_4001.
Percent Change in Adjusted Lung Density
Percent change from baseline to 2 years as measured by centralized, standardized CT lung densitometry. CT scans were acquired at 2 inspiration states: TLC (ie, full inspiration) and FRC (ie, full expiration). Results were adjusted for total lung volume and are presented as point estimates for the average percent change in the early start and delayed start subgroups from an analysis of covariance (ANCOVA) model with country, treatment, and baseline lung density as fixed effects and inspiration state as a repeated random effect. The baseline is the last assessment from the preceding study CE1226_4001.
Change in Subject-reported Symptoms
Patient-reported symptoms were measured using the St George's Respiratory Questionnaire (SGRQ). SGRQ total, symptoms, activity and impact scores range from 0 to 100, with higher scores indicating more limitations, and change from baseline below zero (0) is favorable, indicating improvement.
Percent Change in Lung Function as Measured by Forced Expiratory Volume in 1 Second (FEV1)
Percent Change in Lung Function as Measured by Ratio of FEV1/FVC (Forced Vital Capacity)
Percent Change in Lung Function as Measured by Percent Predicted FEV1
Number of Subjects With Pulmonary Exacerbations
Annual Rate in Subject Years of Pulmonary Exacerbations
Annual exposure-adjusted incidence rate of pulmonary exacerbations.
Time to First Pulmonary Exacerbation
Percentage of Subjects With Treatment Emergent Adverse Events
Percentage of subjects with treatment-emergent adverse events (TEAEs): overall, by severity, by relatedness, by seriousness, and which occurred within 24 hours of Zemaira administration.

Full Information

First Posted
April 29, 2008
Last Updated
July 13, 2016
Sponsor
CSL Behring
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1. Study Identification

Unique Protocol Identification Number
NCT00670007
Brief Title
Extension Study of Zemaira® i.v. Administration in Subjects With Emphysema Due to alpha1-proteinase Inhibitor Deficiency.
Official Title
An Open-label, Non-controlled, Multicenter, Multinational Study to Evaluate the Efficacy and Safety of Zemaira® Administration in Chronic Augmentation and Maintenance Therapy in Subjects With Emphysema Due to alpha1-proteinase Inhibitor Deficiency Who Completed Clinical Study CE1226_4001
Study Type
Interventional

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
April 2008 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring

4. Oversight

5. Study Description

Brief Summary
This study is a continuation of the placebo-controlled study CE1226_4001 (NCT00261833) to evaluate the efficacy and safety of Zemaira® intravenous (i.v). administration in subjects with emphysema due to alpha1-proteinase inhibitor deficiency. The long-term verification of a disease-modifying benefit of Zemaira® on the progression of emphysema will be assessed by volume-adjusted lung density, measured yearly by computed tomography (CT).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Emphysema, Alpha 1-proteinase Inhibitor Deficiency
Keywords
Alpha1-proteinase inhibitor deficiency, Chronic augmentation and maintenance therapy, Emphysema, Emphysema due to Alpha 1-proteinase inhibitor deficiency

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
140 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Zemaira®
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Alpha1- proteinase inhibitor [human]
Other Intervention Name(s)
Zemaira®, Respreeza®
Intervention Description
Lyophilized preparation of 60 mg/kg body weight intravenously once per week
Primary Outcome Measure Information:
Title
Rate of Change of Adjusted Lung Density
Description
As measured by centralized, standardized computer tomographic (CT) lung densitometry. CT scans were acquired at 2 inspiration states: TLC (Total Lung Capacity; ie, full inspiration) and FRC (Functional Residual Capacity; ie, full expiration). Results were adjusted for total lung volume and are presented as point estimates for the average rate of decline in the early start and delayed start subgroups from a linear random regression model with country, inspiration state (only for 'TLC and FRC state'), time (time elapsed since Day 1 [CE1226_4001]), treatment and treatment by time interaction as fixed effects and subject and subject by time interaction as random coefficients.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Absolute Change in Adjusted Lung Density
Description
Absolute change from baseline to 2 years as measured by centralized, standardized CT lung densitometry. CT scans were acquired at 2 inspiration states: TLC (ie, full inspiration) and FRC (ie, full expiration). Results were adjusted for total lung volume and are presented as point estimates for the average absolute change in the early start and delayed start subgroups from an analysis of covariance (ANCOVA) model with country, treatment, and baseline lung density as fixed effects and inspiration state as a repeated random effect. The baseline is the last assessment from the preceding study CE1226_4001.
Time Frame
From baseline to 2 years
Title
Percent Change in Adjusted Lung Density
Description
Percent change from baseline to 2 years as measured by centralized, standardized CT lung densitometry. CT scans were acquired at 2 inspiration states: TLC (ie, full inspiration) and FRC (ie, full expiration). Results were adjusted for total lung volume and are presented as point estimates for the average percent change in the early start and delayed start subgroups from an analysis of covariance (ANCOVA) model with country, treatment, and baseline lung density as fixed effects and inspiration state as a repeated random effect. The baseline is the last assessment from the preceding study CE1226_4001.
Time Frame
From baseline to 2 years
Title
Change in Subject-reported Symptoms
Description
Patient-reported symptoms were measured using the St George's Respiratory Questionnaire (SGRQ). SGRQ total, symptoms, activity and impact scores range from 0 to 100, with higher scores indicating more limitations, and change from baseline below zero (0) is favorable, indicating improvement.
Time Frame
From baseline to 2 years
Title
Percent Change in Lung Function as Measured by Forced Expiratory Volume in 1 Second (FEV1)
Time Frame
From baseline up to 2 years
Title
Percent Change in Lung Function as Measured by Ratio of FEV1/FVC (Forced Vital Capacity)
Time Frame
From baseline up to 2 years
Title
Percent Change in Lung Function as Measured by Percent Predicted FEV1
Time Frame
From baseline up to 2 years
Title
Number of Subjects With Pulmonary Exacerbations
Time Frame
Up to 2 years
Title
Annual Rate in Subject Years of Pulmonary Exacerbations
Description
Annual exposure-adjusted incidence rate of pulmonary exacerbations.
Time Frame
Up to 2 years
Title
Time to First Pulmonary Exacerbation
Time Frame
Up to 2 years
Title
Percentage of Subjects With Treatment Emergent Adverse Events
Description
Percentage of subjects with treatment-emergent adverse events (TEAEs): overall, by severity, by relatedness, by seriousness, and which occurred within 24 hours of Zemaira administration.
Time Frame
From baseline up to 2.5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects who have completed the 2-year treatment and observation period in the Phase 3/4 Zemaira® CE1226_4001 study (NCT00261833) and are willing to sign informed consent Males, and non-pregnant, non-lactating females, whose screening pregnancy test is negative and who are using contraceptive methods deemed reliable by the investigator Exclusion Criteria: Individuals residing in the US Current evidence of alcohol abuse or abuse of drugs such as barbiturates, benzodiazepines, amphetamines, cocaine, opioids, and cannabinoids History of allergy, anaphylactic reaction, or severe systemic response to human plasma derived products, or known mannitol hypersensitivity, or history of prior adverse reaction to mannitol Current tobacco smoker (smoking must be discontinued for at least 6 months prior to study participation) Conditions or behaviors that interfere with attending scheduled study visits in the opinion of the investigator History of non-compliance Administration of any other experimental new drug or participation in an investigation of a marketed product Inability to perform necessary study procedures
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Program Director, Clinical R&D
Organizational Affiliation
CSL Behring
Official's Role
Study Director
Facility Information:
Facility Name
Study Site
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Study Site
City
Fitzroy
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Facility Name
Study Site
City
Darlinghurst
ZIP/Postal Code
2010
Country
Australia
Facility Name
Study Site
City
Nedlands
ZIP/Postal Code
6009
Country
Australia
Facility Name
Study Site
City
New Lambton
ZIP/Postal Code
2305
Country
Australia
Facility Name
Study Site
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6J1S3
Country
Canada
Facility Name
Study Site
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 3A7
Country
Canada
Facility Name
Study Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 2S8
Country
Canada
Facility Name
Study Site
City
Praha 4 - Krc
ZIP/Postal Code
14059
Country
Czech Republic
Facility Name
Study Site
City
Arhus C
ZIP/Postal Code
8000
Country
Denmark
Facility Name
Study Site
City
Hellerup
ZIP/Postal Code
2900
Country
Denmark
Facility Name
Study Site
City
Tartu
ZIP/Postal Code
51014
Country
Estonia
Facility Name
Study Site
City
Oulu
ZIP/Postal Code
90220
Country
Finland
Facility Name
Study Site
City
Essen
ZIP/Postal Code
45239
Country
Germany
Facility Name
Study Site
City
Heidelberg
ZIP/Postal Code
69126
Country
Germany
Facility Name
Study Site
City
Nürnberg
ZIP/Postal Code
90419
Country
Germany
Facility Name
Study Site
City
Dublin
ZIP/Postal Code
9
Country
Ireland
Facility Name
Study Site
City
Krakow
ZIP/Postal Code
31-066
Country
Poland
Facility Name
Study Site
City
Warsaw
ZIP/Postal Code
01-138
Country
Poland
Facility Name
Study Site
City
Bucuresti
ZIP/Postal Code
011026
Country
Romania
Facility Name
Study Site
City
Malmo
ZIP/Postal Code
20502
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
30237305
Citation
Greulich T, Chlumsky J, Wencker M, Vit O, Fries M, Chung T, Shebl A, Vogelmeier C, Chapman KR, McElvaney NG; RAPID Trial Group. Safety of biweekly alpha1-antitrypsin treatment in the RAPID programme. Eur Respir J. 2018 Nov 29;52(5):1800897. doi: 10.1183/13993003.00897-2018. Print 2018 Nov.
Results Reference
derived
PubMed Identifier
27916480
Citation
McElvaney NG, Burdon J, Holmes M, Glanville A, Wark PA, Thompson PJ, Hernandez P, Chlumsky J, Teschler H, Ficker JH, Seersholm N, Altraja A, Makitaro R, Chorostowska-Wynimko J, Sanak M, Stoicescu PI, Piitulainen E, Vit O, Wencker M, Tortorici MA, Fries M, Edelman JM, Chapman KR; RAPID Extension Trial Group. Long-term efficacy and safety of alpha1 proteinase inhibitor treatment for emphysema caused by severe alpha1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE). Lancet Respir Med. 2017 Jan;5(1):51-60. doi: 10.1016/S2213-2600(16)30430-1. Epub 2016 Dec 2. Erratum In: Lancet Respir Med. 2017 Feb;5(2):e13.
Results Reference
derived
PubMed Identifier
26026936
Citation
Chapman KR, Burdon JG, Piitulainen E, Sandhaus RA, Seersholm N, Stocks JM, Stoel BC, Huang L, Yao Z, Edelman JM, McElvaney NG; RAPID Trial Study Group. Intravenous augmentation treatment and lung density in severe alpha1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. Lancet. 2015 Jul 25;386(9991):360-8. doi: 10.1016/S0140-6736(15)60860-1. Epub 2015 May 27.
Results Reference
derived
Links:
URL
http://www.cslbehring.com/clinical-trials/contact-us.htm?registryRefNum=NCT00670007&registryName=ctgov
Description
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Extension Study of Zemaira® i.v. Administration in Subjects With Emphysema Due to alpha1-proteinase Inhibitor Deficiency.

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