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

CSL Behring180 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

180

Conditions

Alpha1-proteinase Inhibitor Deficiency Emphysema

Interventions

Alpha1-proteinase inhibitorBIOLOGICAL

60 mg/kg body weight/week intravenous

PlaceboOTHER

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Locations (28)

Study Site

Denver, Colorado, United States

Outcomes

Primary Outcomes

Annual Rate of Change in Lung Density

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.

Time frame: Over a 2-year period

Secondary Outcomes

Annual Rate of Pulmonary 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. 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.

Time frame: Over a 2-year period

Percent Change in FEV1

Percent change from baseline to Month 24.

Time frame: From baseline to 2 years

Time to First Pulmonary Exacerbation

Time frame: Over a 2-year period

Change in Lung Density

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.

Data from ClinicalTrials.gov

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