Alpha1-proteinase Inhibitor DeficiencyPhase 4NCT00261833
Zemaira in Subjects With Emphysema Due to Alpha1-Proteinase Inhibitor Deficiency
A Phase 4 study testing Alpha1-proteinase inhibitor in people with Alpha1-proteinase Inhibitor Deficiency and Emphysema, run by CSL Behring at 28 sites in 13 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Alpha1-proteinase Inhibitor Deficiency, Emphysema
- What is being tested?
- Alpha1-proteinase inhibitor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 180 participants
- Where
- 28 sitesin 13 countries
- Study dates
- Mar 2006to Sep 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
28 sites in 13 countries.
28 sites in 13 countries
Australia6 sites
Study Site
Adelaide, South Australia, 5000
Study Site
Brisbane, Queensland, 4066
Study Site
Darlinghurst, New South Wales, 2010
Study Site
Fitzroy, 3065
Study Site
Nedlands, Western Australia, 6009
Study Site
New Lambton, New South Wales, 2305
United States4 sites
Study Site
Denver, Colorado, 80206
Study Site
Hershey, Pennsylvania, 17033
Study Site
Miami, Florida, 33136
Study Site
Tyler, Texas, 75708
Germany4 sites
Study Site
Berlin, 12200
Study Site
Essen, 45239
Study Site
Heidelberg, 69126
Study Site
Nuremberg, 90419
Canada3 sites
Study Site
Halifax, Nova Scotia, B3H3A7
Study Site
Toronto, Ontario, M5T2S8
Study Site
Vancouver, British Columbia, V5Z4E1
About this study
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
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).
- Conditions
- Alpha1-proteinase Inhibitor Deficiency, Emphysema
- Being tested
- Alpha1-proteinase inhibitor, Placebo
- Keywords
- Alpha1-proteinase inhibitor deficiency, Emphysema, Chronic augmentation and maintenance therapy
- Medical subject headings
- alpha 1-Antitrypsin Deficiency, Emphysema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alpha1-proteinase inhibitorBiological
Also called Zemaira®
60 mg/kg body weight/week intravenous
PlaceboOther
Lyophilized preparation: 60 mg/kg body weight/week intravenous
| Study group | Role | What they receive |
|---|---|---|
| Zemaira® | Experimental | Not described Receives: Biological: Alpha1-proteinase inhibitor |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Over a 2-year period
Secondary outcomes (12)
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.
Measured: Over a 2-year period
Percent Change in FEV1
Percent change from baseline to Month 24.
Measured: From baseline to 2 years
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.
Measured: Over a 2-year period
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.
Measured: From baseline to 2 years
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).
Measured: From baseline to 2 years
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.
Measured: From baseline to 2 years
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).
Measured: Over a 2-year period
Percent Change in Percent Predicted FEV1
Percent change from baseline to Month 24.
Measured: From baseline to 2 years
Percent Change in FEV1 Divided by Forced Vital Capacity
Percent change from baseline to Month 24.
Measured: From baseline to 2 years
Percent Change in DLCO
Percent change from baseline to Month 24.
Measured: From baseline to 2 years
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.
Measured: Over a 2-year period
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.
Measured: Over a 2-year period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2005 (estimated)
- Study startMar 2006
- Primary completionSep 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alpha1-proteinase Inhibitor DeficiencyStudies of the same condition, open and under way.
- More trials run by CSL BehringThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- CSL Behring
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Senior Director Immonology & Pulmonology, Clinical R&D, Study director, CSL Behring
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00261833
- Sponsor's protocol ID
- CE1226_4001
- Other IDs
- 1449, 2005-003459-12, 2005
- Status last verified
- Jan 2015
- First submitted
- 2 Dec 2005
- Last updated
- 19 Jan 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 30237305Chapman 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.
PubMed 26026936
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00261833
- Acronym / sponsor ID
- CE1226_4001
- Conditions
- Alpha1-proteinase Inhibitor Deficiency, Emphysema
- Keywords
- Alpha1-proteinase inhibitor deficiency, Emphysema, Chronic augmentation and maintenance therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- CSL BehringIndustry (pharma, biotech, devices)
- Study start
- Mar 2006
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 5 Dec 2005 (estimated)
- Results
- Posted 19 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Zemaira® | Experimental | Biological: Alpha1-proteinase inhibitor |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alpha1-proteinase inhibitorAlso: Zemaira®60 mg/kg body weight/week intravenous | Biological | Zemaira® |
| PlaceboLyophilized preparation: 60 mg/kg body weight/week intravenous | Other | Placebo |
Primary outcome
Annual Rate of Change in Lung Density
Time frame: Over a 2-year period
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.
12 secondary outcomes
Annual Rate of Pulmonary Exacerbations
Time frame: Over a 2-year period
Percent Change in FEV1
Time frame: From baseline to 2 years
Time to First Pulmonary Exacerbation
Time frame: Over a 2-year period
Change in Lung Density
Time frame: From baseline to 2 years
Change in Exercise Capacity
Time frame: From baseline to 2 years
Change in Patient-reported Symptoms
Time frame: From baseline to 2 years
Frequency and Intensity of Adverse Events (AEs)
Time frame: Over a 2-year period
Percent Change in Percent Predicted FEV1
Time frame: From baseline to 2 years
Percent Change in FEV1 Divided by Forced Vital Capacity
Time frame: From baseline to 2 years
Percent Change in DLCO
Time frame: From baseline to 2 years
Duration of Pulmonary Exacerbations Relative to Treatment Duration
Time frame: Over a 2-year period
Severity of Pulmonary Exacerbations
Time frame: Over a 2-year period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30237305Greulich 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.
- Derived from this study: PubMed 26026936Chapman 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.
Related trials for Alpha1-proteinase Inhibitor Deficiency
RecruitingObservational study
Role of Genetic Factors in the Development of Lung Disease
Cystic Fibrosis, Pulmonary Fibrosis
RecruitingPhase 1/2
A Study of TSRA-196 in Adults With PiZZ Alpha-1 Antitrypsin Deficiency (AATD)
Alpha-1 Antitrypsin Deficiency (AATD)
RecruitingPhase 4
Genetic Variation in IgG in Alpha 1 Antitrypsin Deficiency
Alpha 1-Antitrypsin, COPD
Enrolling by invitationObservational study
AATD-Liver Scan Study
Alpha-1 Antitrypsin Deficiency, AATD
RecruitingPhase 3
A Non-inferiority Pharmacokinetic and Safety/Tolerability Study of Two Different Doses of Weekly SC Alpha1-PI 15% Compared With Corresponding Standard IV Alpha1-PI in Participants With Alpha1-Antitrypsin Deficiency (AATD)
Alpha 1 Antitrypsin Deficiency
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Senior Director Immonology & Pulmonology, Clinical R&D study director
CSL Behring
28 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Alpha1-proteinase inhibitor in people with Alpha1-proteinase Inhibitor Deficiency and Emphysema, run by CSL Behring at 28 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in Australia, United States, Germany, Canada, Denmark and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Annual Rate of Change in Lung Density (time frame: Over a 2-year period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00261833, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2015.