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

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).

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.