Zemaira in Subjects With Emphysema Due to Alpha1-Proteinase Inhibitor Deficiency

January 11, 2015 updated by: CSL Behring

A Randomized, Placebo-Controlled, Double-Blind, Multicenter Phase III/IV Study to Compare the Efficacy and Safety of 60mg/kg Body Weight of Zemaira® Weekly I.V. Administration With Placebo Weekly I.V. Administration in Chronic Augmentation and Maintenance Therapy in Subjects With Emphysema Due to Alpha1-Proteinase Inhibitor Deficiency

This is a randomized, placebo-controlled, double-blind, multicenter phase III/IV study to compare the efficacy and safety of Zemaira® with placebo in subjects with emphysema due to alpha1-proteinase inhibitor deficiency. The effect of Zemaira® on the progression of emphysema will be assessed by the decline of lung density, measured by computed tomography (CT).

Study Overview

Study Type

Interventional

Enrollment (Actual)

180

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Fitzroy, Australia, 3065
        • Study site
    • New South Wales
      • Darlinghurst, New South Wales, Australia, 2010
        • Study site
      • New Lambton, New South Wales, Australia, 2305
        • Study site
    • Queensland
      • Brisbane, Queensland, Australia, 4066
        • Study site
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Study site
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Study site
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z4E1
        • Study site
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H3A7
        • Study site
    • Ontario
      • Toronto, Ontario, Canada, M5T2S8
        • Study site
      • Praha, Czech Republic, 14059
        • Study site
      • Arhus, Denmark, 8000
        • Study site
      • Hellerup, Denmark, 2900
        • Study site
      • Tartu, Estonia, 51014
        • Study site
      • Oulu, Finland, 90220
        • Study site
      • Berlin, Germany, 12200
        • Study site
      • Essen, Germany, 45239
        • Study site
      • Heidelberg, Germany, 69126
        • Study site
      • Nürnberg, Germany, 90419
        • Study site
      • Dublin, Ireland, 9
        • Study site
      • Krakow, Poland, 31-066
        • Study site
      • Warsaw, Poland, 01-138
        • Study site
      • Bucuresti, Romania, 011026
        • Study site
      • Barnaul, Russian Federation
        • Study site
      • Malmo, Sweden, 20502
        • Study site
    • Colorado
      • Denver, Colorado, United States, 80206
        • Study site
    • Florida
      • Miami, Florida, United States, 33136
        • Study site
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Study site
    • Texas
      • Tyler, Texas, United States, 75708
        • Study site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 18 to 65 years of age and willing to sign informed consent.
  • Males and non-pregnant, non-lactating females whose screening pregnancy test is negative and who are using contraceptives methods deemed reliable by the investigator.
  • Diagnosis of alpha1-proteinase inhibitor (A1-PI) deficiency (serum A1-PI levels < 11 μM or < 80 mg/dL). This includes newly diagnosed subjects, previously untreated subjects, currently treated subjects, and subjects currently not on treatment therapy but on treatment in the past.
  • Subjects with emphysema and forced expiratory volume in 1 second (FEV1) ≥ 35% and ≤ 70% (predicted).
  • No signs of chronic or acute Hepatitis A, Hepatitis B, Hepatitis C or HIV infection (negative serologies for HIV and viral hepatitis). In case of positive serologies for viral hepatitis, vaccination status or negative IgM should be available.

Exclusion Criteria:

  • Any relevant chronic diseases or history of relevant diseases (e.g., severe renal insufficiency) except respiratory or liver disease secondary to alpha1-proteinase inhibitor deficiency. Subjects with well-controlled, chronic diseases may be included after consultation with the treating physician and the sponsor.
  • Current evidence of alcohol abuse or history of abuse of illegal and/or legally prescribed 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.
  • History of transfusion reactions.
  • Selective IgA deficiency.
  • Acute illness within one week prior to the first administration of the investigational medicinal product (IMP). Start of treatment after recovery is possible.
  • Current tobacco smoker (smoking has to be ceased at least 6 months prior study inclusion). Subjects with a positive cotinine test due to nicotine replacement therapy (e.g. patches, chewing gum) or snuff are eligible.
  • 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 within one month prior to the screening visit date.
  • Inability to perform necessary study procedures.
  • Lung transplantation, lung volume reduction surgery or lobectomy or being on a waiting list for any such surgeries.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Lyophilized preparation: 60 mg/kg body weight/week intravenous
Experimental: Zemaira®
60 mg/kg body weight/week intravenous
Other Names:
  • Zemaira®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annual Rate of Change in Lung Density
Time Frame: Over a 2-year period
As measured by centralized, standardized computer tomographic (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 rate of decline in each treatment group.
Over a 2-year period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annual Rate of Pulmonary Exacerbations
Time Frame: Over a 2-year period
Primary diagnostic criteria for exacerbations were increased dyspnea, increased sputum volume, and increased sputum purulence. Supporting diagnostic criteria were upper respiratory tract infection, fever without other apparent cause, increased wheezing, and increased cough. For diagnosis, participants had to meet 2 of the 3 primary criteria or 1 primary criterion and 1 supporting criterion. The annual rate was based on the total number of exacerbations and the total number of participant study days for all participants in the specified analysis population and adjusted to 365.25 days.
Over a 2-year period
Percent Change in FEV1
Time Frame: From baseline to 2 years
Percent change from baseline to Month 24.
From baseline to 2 years
Time to First Pulmonary Exacerbation
Time Frame: Over a 2-year period
Primary diagnostic criteria for exacerbations were increased dyspnea, increased sputum volume, and increased sputum purulence. Supporting diagnostic criteria were upper respiratory tract infection, fever without other apparent cause, increased wheezing, and increased cough. For diagnosis, participants had to meet 2 of the 3 primary criteria or 1 primary criterion and 1 supporting criterion.
Over a 2-year period
Change in Lung Density
Time Frame: From baseline to 2 years
Change from baseline to Month 24 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.
From baseline to 2 years
Change in Exercise Capacity
Time Frame: From baseline to 2 years
Exercise capacity was measured as distance walked, using the incremental shuttle walk test. Change from baseline to end of treatment (2 years) in exercise capacity was analysed using an analysis of covariance (ANCOVA).
From baseline to 2 years
Change in Patient-reported Symptoms
Time Frame: From baseline to 2 years
Patient-reported symptoms were measured using the symptoms score component of the St George's Respiratory Questionnaire (SGRQ). SGRQ scores range from 0 to 100, with higher scores indicating more limitations and negative values for change indicating improvement. Change from baseline to end of treatment (2 years) in SGRQ was analysed using an ANCOVA.
From baseline to 2 years
Frequency and Intensity of Adverse Events (AEs)
Time Frame: Over a 2-year period
Number of participants with at least one AE, and the number of participants with mild, moderate or severe AEs. AE intensity was defined as mild (does not interfere with routine activities), moderate (interferes with routine activities), or severe (impossible to perform routine activities).
Over a 2-year period
Percent Change in Percent Predicted FEV1
Time Frame: From baseline to 2 years
Percent change from baseline to Month 24.
From baseline to 2 years
Percent Change in FEV1 Divided by Forced Vital Capacity
Time Frame: From baseline to 2 years
Percent change from baseline to Month 24.
From baseline to 2 years
Percent Change in DLCO
Time Frame: From baseline to 2 years
Percent change from baseline to Month 24.
From baseline to 2 years
Duration of Pulmonary Exacerbations Relative to Treatment Duration
Time Frame: Over a 2-year period
Defined as the percentage of total treatment duration across participants for 1) exacerbations overall, 2) antibiotic treatment for exacerbations, and 3) hospitalization for exacerbations. Primary diagnostic criteria for exacerbations were increased dyspnea, increased sputum volume, and increased sputum purulence. Supporting diagnostic criteria were upper respiratory tract infection, fever without other apparent cause, increased wheezing, and increased cough. For diagnosis, participants had to meet 2 of the 3 primary criteria or 1 primary criterion and 1 supporting criterion.
Over a 2-year period
Severity of Pulmonary Exacerbations
Time Frame: Over a 2-year period

Defined as the number of participants requiring 1) antibiotic treatment for exacerbations, and 2) hospitalization for exacerbations. Primary diagnostic criteria for exacerbations were increased dyspnea, increased sputum volume, and increased sputum purulence. Supporting diagnostic criteria were upper respiratory tract infection, fever without other apparent cause, increased wheezing, and increased cough. For diagnosis, participants had to meet 2 of the 3 primary criteria or 1 primary criterion and 1 supporting criterion.

Antibiotic treatment usage was reported by quarterly interval.

Over a 2-year period

Other Outcome Measures

Outcome Measure
Time Frame
Baseline Lung Density at Total Lung Capacity (TLC) and Forced Residual Capacity (FRC)
Time Frame: Baseline
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: Senior Director Immonology & Pulmonology, Clinical R&D, CSL Behring

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2006

Primary Completion (Actual)

September 1, 2012

Study Completion (Actual)

September 1, 2012

Study Registration Dates

First Submitted

December 2, 2005

First Submitted That Met QC Criteria

December 2, 2005

First Posted (Estimate)

December 5, 2005

Study Record Updates

Last Update Posted (Estimate)

January 19, 2015

Last Update Submitted That Met QC Criteria

January 11, 2015

Last Verified

January 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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