Chronic augmentation and maintenance therapy in individuals with alpha1-proteinase inhibitor (A1-PI) deficiency and clinical evidence of emphysema. MedDRA version: 14.1 Level: LLT Classification code 10001811 Term: Alpha-1 proteinase inhibitor deficiency System Organ Class: 100000004850
Conditions
Interventions
Product Name: Alpha1-Proteinase Inhibitor / Zemaira®
Product Code: CE1226
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: There is no recommended INN.
Current S
Sponsors
CSL Behring GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 18 to 65 years of age and willing to sign informed consent. 2. Males, and non-pregnant, non-lactating females, whose screening pregnancy test is negative and who are using contraceptive methods deemed reliable by the investigator. 3. Diagnosis of alpha1-proteinase inhibitor deficiency (serum A1- PI levels 35 and =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. 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. 2. 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. 3. 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. 4. History of transfusion reactions. 5. Selective IgA deficiency. 6. Acute illness within one week prior to the first administration of the investigational medicinal product (IMP). Start of treatment after recovery is possible. 7. 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. 8. Conditions or behaviors that interfere with attending scheduled study visits in opinion of the investigator. 9. History of non-compliance. 10. 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. 11. Inability to perform necessary study procedures. 12. Lung transplantation, lung volume reduction surgery or lobectomy or being on a waiting list for any such surgeries.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effect of Zemaira® on the progression of emphysema, assessed by the decline of lung density, measured by computed tomography (CT).;Secondary Objective: The key secondary objectives are to assess the effect of treatment with A1-PI on the following clinical assessments: 1. Change in exercise capacity assessed by the Incremental Shuttle Walking Test (ISWT) 2. Change in symptoms assessed by the St. George’s Respiratory Questionnaire (SGRQ) 3. The rate of pulmonary exacerbations Additional secondary objectives include the assessment of the effect of A1-PI on pulmonary function test parameters.;Primary end point(s): Annual rate of change of lung volume-adjusted lung density that is estimated by the P15 value from CT scans, as measured by the slope of time and treatment interaction from a mixed effects model;Timepoint(s) of evaluation of this end point: See E.5.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Efficacy Endpoints: · Change in exercise capacity as measured by change from baseline to month 24 of distance walked in the ISWT · Change in symptoms score as measured by change from baseline to month 24 of symptom domain in the SGRQ · Annual rate of pulmonary exacerbations over 2 years Other Secondary Efficacy Endpoints: · Adjusted P15 values, change from baseline to month 24 based on CT scans · The percent change from baseline to month 24 of pulmonary function test assessments (forced expiratory flow volume in 1 second [FEV1], FEV1 as a percentage of predicted, FEV1 as a proportion of forced vital capacity [FVC], and diffusion capacity of carbon monoxide [DLCO] · Characteristics of pulmonary exacerbations: - Time to first event - Duration and severity as measured by: Exacerbation days Requiring antibiotics (intravenous, oral) Requiring hospitalization Hospitalization days Antibiotic usage;Timepoint(s) of evaluation of this end point: See E.5.2 | — |
Countries
Australia, Bulgaria, Canada, Czech Republic, Denmark, Estonia, Finland, Germany, Ireland, Poland, Romania, Sweden, United States
Contacts
Public ContactTrial Disclosure Manager
CSL Behring GmbH
Outcome results
None listed