Zemaira in Subjects With Emphysema Due to Alpha1-Proteinase Inhibitor Deficiency
Condition: Alpha1-proteinase Inhibitor Deficiency; Emphysema
MeSH terms: Alpha 1-Antitrypsin Deficiency; Pulmonary Emphysema; Emphysema
Intervention: Alpha1-proteinase inhibitor; Placebo
Intervention description: 60 mg/kg body weight/week intravenous; Lyophilized preparation: 60 mg/kg body weight/week intravenous
Intervention MeSH terms: Protease Inhibitors; Alpha 1-Antitrypsin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 180.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Alpha1-proteinase inhibitor deficiency; Emphysema; Chronic augmentation and maintenance therapy

Summary:

      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).
    

Eligibility criteria:

        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.