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

• ClinicalTrials.gov Identifier: NCT00670007
• Recruitment Status: Completed
• First Posted: May 1, 2008
• Results First Posted: July 12, 2016
• Last Update Posted: August 15, 2016
• Sponsor: CSL Behring
• Information provided by (Responsible Party): CSL Behring

Tracking Information

• First Submitted Date: April 29, 2008
• First Posted Date: May 1, 2008
• Results First Submitted Date: June 2, 2016
• Results First Posted Date: July 12, 2016
• Last Update Posted Date: August 15, 2016
• Study Start Date: April 2008
• Actual Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 2, 2016)

Rate of Change of Adjusted Lung Density [ Time Frame: Up to 2 years ]

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.

• Original Primary Outcome Measures (submitted: April 30, 2008): Lung Density measured by CT scans [ Time Frame: Yearly ]

Current Secondary Outcome Measures (submitted: July 13, 2016)

• Absolute Change in Adjusted Lung Density [ Time Frame: From baseline to 2 years ]
  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 [ Time Frame: From baseline to 2 years ]
  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 [ Time Frame: From baseline to 2 years ]
  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) [ Time Frame: From baseline up to 2 years ]
• Percent Change in Lung Function as Measured by Ratio of FEV1/FVC (Forced Vital Capacity) [ Time Frame: From baseline up to 2 years ]
• Percent Change in Lung Function as Measured by Percent Predicted FEV1 [ Time Frame: From baseline up to 2 years ]
• Number of Subjects With Pulmonary Exacerbations [ Time Frame: Up to 2 years ]
• Annual Rate in Subject Years of Pulmonary Exacerbations [ Time Frame: Up to 2 years ]
  Annual exposure-adjusted incidence rate of pulmonary exacerbations.
• Time to First Pulmonary Exacerbation [ Time Frame: Up to 2 years ]
• Percentage of Subjects With Treatment Emergent Adverse Events [ Time Frame: From baseline up to 2.5 years ]
  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.

Original Secondary Outcome Measures (submitted: April 30, 2008)

• Pulmonary Exacerbations [ Time Frame: ongoing ]
• Pulmonary Function [ Time Frame: Quarterly ]
• Antigenic and functional serum A1 - PI Levels [ Time Frame: Quarterly ]
• Body mass index [ Time Frame: Quarterly ]
• Quality of Life [ Time Frame: Yearly ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Emphysema
• Alpha 1-proteinase Inhibitor Deficiency

Intervention

Biological: Alpha1- proteinase inhibitor [human]

Lyophilized preparation of 60 mg/kg body weight intravenously once per week

Other Names:

• Zemaira®
• Respreeza®

Study Arms

Experimental: Zemaira®

Intervention: Biological: Alpha1- proteinase inhibitor [human]

Publications *

• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 10, 2013): 140
• Original Estimated Enrollment (submitted: April 30, 2008): 100
• Actual Study Completion Date: September 2014
• Actual Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Czech Republic, Denmark, Estonia, Finland, Germany, Ireland, Poland, Romania, Sweden

Administrative Information

• NCT Number: NCT00670007
• Other Study ID Numbers: CE1226_3001; 1466 ( Other Identifier: CSL Behring ); 2007-007129-38 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: CSL Behring
• Original Responsible Party: Thomas S. Mingot, CSL Behring
• Current Study Sponsor: CSL Behring
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Program Director, Clinical R&D; CSL Behring

• PRS Account: CSL Behring
• Verification Date: July 2016