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Completed

NCT Number: NCT00261833

Zemaira 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).

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Key information

Conditions

Alpha1-Proteinase Inhibitor Deficiency Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Emphysema Genetic Diseases, Inborn Liver Diseases Lung Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases Subcutaneous Emphysema alpha 1-Antitrypsin Deficiency

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Study Site, Darlinghurst, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Alpha1-Proteinase Inhibitor

Biological

60 mg/kg body weight/week intravenous

Other names: Zemaira®

Placebo

Other

Lyophilized preparation: 60 mg/kg body weight/week intravenous

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. Percent Change in FEV1

    Time frame: From baseline to 2 years

    Percent change from baseline to Month 24.

  3. 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.

  4. 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.

  5. 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).

  6. 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.

  7. 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).

  8. Percent Change in Percent Predicted FEV1

    Time frame: From baseline to 2 years

    Percent change from baseline to Month 24.

  9. Percent Change in FEV1 Divided by Forced Vital Capacity

    Time frame: From baseline to 2 years

    Percent change from baseline to Month 24.

  10. Percent Change in DLCO

    Time frame: From baseline to 2 years

    Percent change from baseline to Month 24.

  11. 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.

  12. 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.

Other outcomes

  1. Baseline Lung Density at Total Lung Capacity (TLC) and Forced Residual Capacity (FRC)

    Time frame: Baseline

Sponsors and collaborators

Lead sponsor

CSL Behring

Industry

Registry information

Official study title

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

Important dates

Study start
2006
Primary completion
2012
Study completion
2012
First posted
Dec 5, 2005
Registry last updated
Jan 19, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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