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

Emphysema Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00261833
• Other study ID #: CE1226_4001
• Secondary ID: 14492005-003459-
• Status: Completed
• Phase: Phase 4
• First received: December 2, 2005
• Last updated: January 11, 2015
• Start date: March 2006
• Est. completion date: September 2012

Study information

• Verified date: January 2015
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustralia: Department of Health and Ageing Therapeutic Goods AdministrationCanada: Ethics Review CommitteeCanada: Health CanadaCzech Republic: Ethics CommitteeCzech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyDenmark: Ethics CommitteeDenmark: The Danish National Committee on Biomedical Research EthicsEstonia: The State Agency of MedicineFinland: Ethics CommitteeFinland: Finnish Medicines AgencyGermany: Ethics CommissionGermany: Paul-Ehrlich-InstitutIreland: Irish Medicines BoardIreland: Medical Ethics Research CommitteePoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRomania: National Medicines AgencySweden: Medical Products Agency
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alpha 1-Antitrypsin Deficiency
• Alpha1-proteinase Inhibitor Deficiency
• Emphysema
• Pulmonary Emphysema

Intervention

Biological:
• Alpha1-proteinase inhibitor
60 mg/kg body weight/week intravenous

Other:
• Placebo
Lyophilized preparation: 60 mg/kg body weight/week intravenous

Locations

Country	Name	City	State
Australia	Study Site	Adelaide	South Australia
Australia	Study Site	Brisbane	Queensland
Australia	Study Site	Darlinghurst	New South Wales
Australia	Study Site	Fitzroy
Australia	Study Site	Nedlands	Western Australia
Australia	Study Site	New Lambton	New South Wales
Canada	Study Site	Halifax	Nova Scotia
Canada	Study Site	Toronto	Ontario
Canada	Study Site	Vancouver	British Columbia
Czech Republic	Study Site	Praha
Denmark	Study Site	Arhus
Denmark	Study Site	Hellerup
Estonia	Study Site	Tartu
Finland	Study Site	Oulu
Germany	Study Site	Berlin
Germany	Study Site	Essen
Germany	Study Site	Heidelberg
Germany	Study Site	Nürnberg
Ireland	Study Site	Dublin
Poland	Study Site	Krakow
Poland	Study Site	Warsaw
Romania	Study Site	Bucuresti
Russian Federation	Study Site	Barnaul
Sweden	Study Site	Malmo
United States	Study Site	Denver	Colorado
United States	Study Site	Hershey	Pennsylvania
United States	Study Site	Miami	Florida
United States	Study Site	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czech Republic,  Denmark,  Estonia,  Finland,  Germany,  Ireland,  Poland,  Romania,  Russian Federation,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Baseline Lung Density at Total Lung Capacity (TLC) and Forced Residual Capacity (FRC)		Baseline	No
Primary	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.	Over a 2-year period	No
Secondary	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.	Over a 2-year period	No
Secondary	Percent Change in FEV1	Percent change from baseline to Month 24.	From baseline to 2 years	No
Secondary	Time to First Pulmonary Exacerbation	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.	Over a 2-year period	No
Secondary	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.	From baseline to 2 years	No
Secondary	Change in Exercise Capacity	Exercise capacity was measured as distance walked, using the incremental shuttle walk test. Change from baseline to end of treatment (2 years) in exercise capacity was analysed using an analysis of covariance (ANCOVA).	From baseline to 2 years	No
Secondary	Change in Patient-reported Symptoms	Patient-reported symptoms were measured using the symptoms score component of the St George's Respiratory Questionnaire (SGRQ). SGRQ scores range from 0 to 100, with higher scores indicating more limitations and negative values for change indicating improvement. Change from baseline to end of treatment (2 years) in SGRQ was analysed using an ANCOVA.	From baseline to 2 years	No
Secondary	Frequency and Intensity of Adverse Events (AEs)	Number of participants with at least one AE, and the number of participants with mild, moderate or severe AEs. AE intensity was defined as mild (does not interfere with routine activities), moderate (interferes with routine activities), or severe (impossible to perform routine activities).	Over a 2-year period	Yes
Secondary	Percent Change in Percent Predicted FEV1	Percent change from baseline to Month 24.	From baseline to 2 years	No
Secondary	Percent Change in FEV1 Divided by Forced Vital Capacity	Percent change from baseline to Month 24.	From baseline to 2 years	No
Secondary	Percent Change in DLCO	Percent change from baseline to Month 24.	From baseline to 2 years	No
Secondary	Duration of Pulmonary Exacerbations Relative to Treatment Duration	Defined as the percentage of total treatment duration across participants for 1) exacerbations overall, 2) antibiotic treatment for exacerbations, and 3) hospitalization for 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.	Over a 2-year period	No
Secondary	Severity of Pulmonary Exacerbations	Defined as the number of participants requiring 1) antibiotic treatment for exacerbations, and 2) hospitalization for 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.; Antibiotic treatment usage was reported by quarterly interval.	Over a 2-year period	No

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