Phase 4
N=180
Zemaira in Subjects With Emphysema Due to Alpha1-Proteinase Inhibitor Deficiency
Alpha1-proteinase Inhibitor Deficiency · Emphysema
Bottom Line
View on ClinicalTrials.gov: NCT00261833 ↗Enrolled (actual)
180
Serious AEs
31.1%
Results posted
Jan 2015
Primary outcome: Primary: Annual Rate of Change in Lung Density — -1.50; -2.12; -1.45; -2.19 g/L per year — p=0.029
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Alpha1-proteinase inhibitor (Biological); Placebo (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- CSL Behring
- Primary completion
- Sep 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Annual Rate of Change in Lung Density |
-1.50; -2.12; -1.45; -2.19; -1.55; -2.02 | 0.029 sig |
| SECONDARY Annual Rate of Pulmonary Exacerbations |
1.70; 1.42 | — |
| SECONDARY Percent Change in FEV1 |
-4.29; -2.06 | — |
| SECONDARY Time to First Pulmonary Exacerbation |
0.60; 0.73 | — |
| SECONDARY Change in Lung Density |
-2.33; -3.37; -2.22; -3.54; -2.44; -3.33 | 0.058 |
| SECONDARY Change in Exercise Capacity |
1.77; 14.86 | — |
| SECONDARY Change in Patient-reported Symptoms |
-1.19; -0.09 | — |
| SECONDARY Frequency and Intensity of Adverse Events (AEs) |
92; 86; 13; 16; 54; 43 | — |
| SECONDARY Percent Change in Percent Predicted FEV1 |
-4.16; -1.90 | — |
| SECONDARY Percent Change in FEV1 Divided by Forced Vital Capacity |
-2.68; 1.56 | — |
| SECONDARY Percent Change in DLCO |
-3.16; -1.85 | — |
| SECONDARY Duration of Pulmonary Exacerbations Relative to Treatment Duration |
77.2; 58.9; 6.32; 5.55; 6.22; 2.16 | — |
| SECONDARY Severity of Pulmonary Exacerbations |
13; 9; 80; 78; 10; 5 | — |
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.
Data sourced from ClinicalTrials.gov (NCT00261833). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.