Clinical trial NCT00261833: Zemaira in Subjects With Emphysema Due to Alpha1-Proteinase Inhibitor Deficiency
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Alpha1-proteinase Inhibitor Deficiency
Emphysema
Keywords: Alpha1-proteinase inhibitor deficiency
Emphysema
Chronic augmentation and maintenance therapy
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2005-12-05
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Annual Rate of Change in Lung Density
timeFrame: Over a 2-year period
Secondary outcomes:
measure: Annual Rate of Pulmonary Exacerbations
timeFrame: Over a 2-year period
measure: Percent Change in FEV1
timeFrame: From baseline to 2 years
measure: Time to First Pulmonary Exacerbation
timeFrame: Over a 2-year period
measure: Change in Lung Density
timeFrame: From baseline to 2 years
measure: Change in Exercise Capacity
timeFrame: From baseline to 2 years
measure: Change in Patient-reported Symptoms
timeFrame: From baseline to 2 years
measure: Frequency and Intensity of Adverse Events (AEs)
timeFrame: Over a 2-year period
measure: Percent Change in Percent Predicted FEV1
timeFrame: From baseline to 2 years
measure: Percent Change in FEV1 Divided by Forced Vital Capacity
timeFrame: From baseline to 2 years
measure: Percent Change in DLCO
timeFrame: From baseline to 2 years
measure: Duration of Pulmonary Exacerbations Relative to Treatment Duration
timeFrame: Over a 2-year period
measure: Severity of Pulmonary Exacerbations
timeFrame: Over a 2-year period
Other outcomes:
measure: Baseline Lung Density at Total Lung Capacity (TLC) and Forced Residual Capacity (FRC)
timeFrame: Baseline
Locations:
city: Denver
country: United States
facility: Study Site
state: Colorado
city: Miami
country: United States
facility: Study Site
state: Florida
city: Hershey
country: United States
facility: Study Site
state: Pennsylvania
city: Tyler
country: United States
facility: Study Site
state: Texas
city: Darlinghurst
country: Australia
facility: Study Site
state: New South Wales
city: New Lambton
country: Australia
facility: Study Site
state: New South Wales
city: Brisbane
country: Australia
facility: Study Site
state: Queensland
city: Adelaide
country: Australia
facility: Study Site
state: South Australia
city: Nedlands
country: Australia
facility: Study Site
state: Western Australia
city: Fitzroy
country: Australia
facility: Study Site
city: Vancouver
country: Canada
facility: Study Site
state: British Columbia
city: Halifax
country: Canada
facility: Study Site
state: Nova Scotia
city: Toronto
country: Canada
facility: Study Site
state: Ontario
city: Praha
country: Czech Republic
facility: Study Site
city: Arhus
country: Denmark
facility: Study Site
city: Hellerup
country: Denmark
facility: Study Site
city: Tartu
country: Estonia
facility: Study Site
city: Oulu
country: Finland
facility: Study Site
city: Berlin
country: Germany
facility: Study Site
city: Essen
country: Germany
facility: Study Site
city: Heidelberg
country: Germany
facility: Study Site
city: Nürnberg
country: Germany
facility: Study Site
city: Dublin
country: Ireland
facility: Study Site
city: Krakow
country: Poland
facility: Study Site
city: Warsaw
country: Poland
facility: Study Site
city: Bucuresti
country: Romania
facility: Study Site
city: Barnaul
country: Russian Federation
facility: Study Site
city: Malmo
country: Sweden
facility: Study Site
Study officials:
affiliation: CSL Behring
name: Senior Director Immonology & Pulmonology, Clinical R&D
role: STUDY_DIRECTOR
References:
citation: Greulich T, Chlumsky J, Wencker M, Vit O, Fries M, Chung T, Shebl A, Vogelmeier C, Chapman KR, McElvaney NG; RAPID Trial Group. Safety of biweekly alpha1-antitrypsin treatment in the RAPID programme. Eur Respir J. 2018 Nov 29;52(5):1800897. doi: 10.1183/13993003.00897-2018. Print 2018 Nov.
citation: Chapman KR, Burdon JG, Piitulainen E, Sandhaus RA, Seersholm N, Stocks JM, Stoel BC, Huang L, Yao Z, Edelman JM, McElvaney NG; RAPID Trial Study Group. Intravenous augmentation treatment and lung density in severe alpha1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. Lancet. 2015 Jul 25;386(9991):360-8. doi: 10.1016/S0140-6736(15)60860-1. Epub 2015 May 27.