EmphysemaPhase 4NCT00670007
Extension Study of Zemaira® i.v. Administration in Subjects With Emphysema Due to alpha1-proteinase Inhibitor Deficiency.
A Phase 4 study testing Alpha1- proteinase inhibitor [human] in people with Emphysema and Alpha 1-proteinase Inhibitor Deficiency, run by CSL Behring at 21 sites in 11 countries.
Trial summary
This study is a continuation of the placebo-controlled study CE1226_4001 (NCT00261833) to evaluate the efficacy and safety of Zemaira® intravenous (i.v). administration in subjects with emphysema due to alpha1-proteinase inhibitor deficiency. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Emphysema, Alpha 1-proteinase Inhibitor Deficiency
- What is being tested?
- Alpha1- proteinase inhibitor [human]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 21 sitesin 11 countries
- Study dates
- Apr 2008to Sep 2014
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects who have completed the 2-year treatment and observation period in the Phase 3/4 Zemaira® CE1226_4001 study (NCT00261833) and are willing to sign informed consent
- Males, and non-pregnant, non-lactating females, whose screening pregnancy test is negative and who are using contraceptive methods deemed reliable by the investigator
Who cannot join
- Individuals residing in the US
- Current evidence of alcohol abuse or abuse of 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
- Current tobacco smoker (smoking must be discontinued for at least 6 months prior to study participation)
- 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
- Inability to perform necessary study procedures
Trial locations and contacts
21 sites in 11 countries.
21 sites in 11 countries
Australia5 sites
Study Site
Adelaide, South Australia, 5000
Study Site
Darlinghurst, 2010
Study Site
Fitzroy, Victoria, 3065
Study Site
Nedlands, 6009
Study Site
New Lambton, 2305
Canada3 sites
Study Site
Halifax, Nova Scotia, B3H 3A7
Study Site
Toronto, Ontario, M5T 2S8
Study Site
Vancouver, British Columbia, V6J1S3
Germany3 sites
Study Site
Essen, 45239
Study Site
Heidelberg, 69126
Study Site
Nuremberg, 90419
About this study
Official title: An Open-label, Non-controlled, Multicenter, Multinational Study to Evaluate the Efficacy and Safety of Zemaira® Administration in Chronic Augmentation and Maintenance Therapy in Subjects With Emphysema Due to alpha1-proteinase Inhibitor Deficiency Who Completed Clinical Study CE1226_4001
This study is a continuation of the placebo-controlled study CE1226_4001 (NCT00261833) to evaluate the efficacy and safety of Zemaira® intravenous (i.v). administration in subjects with emphysema due to alpha1-proteinase inhibitor deficiency. The long-term verification of a disease-modifying benefit of Zemaira® on the progression of emphysema will be assessed by volume-adjusted lung density, measured yearly by computed tomography (CT).
- Conditions
- Emphysema, Alpha 1-proteinase Inhibitor Deficiency
- Being tested
- Alpha1- proteinase inhibitor [human]
- Keywords
- Alpha1-proteinase inhibitor deficiency, Chronic augmentation and maintenance therapy, Emphysema, Emphysema due to Alpha 1-proteinase inhibitor deficiency
- Medical subject headings
- Emphysema, alpha 1-Antitrypsin Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alpha1- proteinase inhibitor [human]Biological
Also called Zemaira®, Respreeza®
Lyophilized preparation of 60 mg/kg body weight intravenously once per week
| Study group | Role | What they receive |
|---|---|---|
| Zemaira® | Experimental | Not described Receives: Biological: Alpha1- proteinase inhibitor [human] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Change of Adjusted Lung Density
As measured by centralized, standardized computer tomographic (CT) lung densitometry. CT scans were acquired at 2 inspiration states: TLC (Total Lung Capacity; ie, full inspiration) and FRC (Functional Residual Capacity; ie, full expiration). Results were adjusted for total lung volume and are presented as point estimates for the average rate of decline in the early start and delayed start subgroups from a linear random regression model with country, inspiration state (only for 'TLC and FRC state'), time (time elapsed since Day 1 [CE1226_4001]), treatment and treatment by time interaction as fixed effects and subject and subject by time interaction as random coefficients.
Measured: Up to 2 years
Secondary outcomes (10)
Absolute Change in Adjusted Lung Density
Absolute change from baseline to 2 years 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 and are presented as point estimates for the average absolute change in the early start and delayed start subgroups from an analysis of covariance (ANCOVA) model with country, treatment, and baseline lung density as fixed effects and inspiration state as a repeated random effect. The baseline is the last assessment from the preceding study CE1226_4001.
Measured: From baseline to 2 years
Percent Change in Adjusted Lung Density
Percent change from baseline to 2 years 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 and are presented as point estimates for the average percent change in the early start and delayed start subgroups from an analysis of covariance (ANCOVA) model with country, treatment, and baseline lung density as fixed effects and inspiration state as a repeated random effect. The baseline is the last assessment from the preceding study CE1226_4001.
Measured: From baseline to 2 years
Change in Subject-reported Symptoms
Patient-reported symptoms were measured using the St George's Respiratory Questionnaire (SGRQ). SGRQ total, symptoms, activity and impact scores range from 0 to 100, with higher scores indicating more limitations, and change from baseline below zero (0) is favorable, indicating improvement.
Measured: From baseline to 2 years
Percent Change in Lung Function as Measured by Forced Expiratory Volume in 1 Second (FEV1)
Measured: From baseline up to 2 years
Percent Change in Lung Function as Measured by Ratio of FEV1/FVC (Forced Vital Capacity)
Measured: From baseline up to 2 years
Percent Change in Lung Function as Measured by Percent Predicted FEV1
Measured: From baseline up to 2 years
Number of Subjects With Pulmonary Exacerbations
Measured: Up to 2 years
Annual Rate in Subject Years of Pulmonary Exacerbations
Annual exposure-adjusted incidence rate of pulmonary exacerbations.
Measured: Up to 2 years
Time to First Pulmonary Exacerbation
Measured: Up to 2 years
Percentage of Subjects With Treatment Emergent Adverse Events
Percentage of subjects with treatment-emergent adverse events (TEAEs): overall, by severity, by relatedness, by seriousness, and which occurred within 24 hours of Zemaira administration.
Measured: From baseline up to 2.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2008 (estimated)
- Study startApr 2008
- Primary completionSep 2014
- Study completionSep 2014
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 (3)Papers the sponsor has linked to this study.
- Other trials for EmphysemaStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- CSL Behring
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Program Director, Clinical R&D, Study director, CSL Behring
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00670007
- Sponsor's protocol ID
- CE1226_3001
- Other IDs
- 1466, 2007-007129-38
- Status last verified
- Jul 2016
- First submitted
- 29 Apr 2008
- Last updated
- 15 Aug 2016
- Results posted
- Yes, on ClinicalTrials.gov
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 30237305McElvaney NG, Burdon J, Holmes M, Glanville A, Wark PA, Thompson PJ, Hernandez P, Chlumsky J, Teschler H, Ficker JH, Seersholm N, Altraja A, Makitaro R, Chorostowska-Wynimko J, Sanak M, Stoicescu PI, Piitulainen E, Vit O, Wencker M, Tortorici MA, Fries M, Edelman JM, Chapman KR; RAPID Extension Trial Group. Long-term efficacy and safety of alpha1 proteinase inhibitor treatment for emphysema caused by severe alpha1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE). Lancet Respir Med. 2017 Jan;5(1):51-60. doi: 10.1016/S2213-2600(16)30430-1. Epub 2016 Dec 2.
PubMed 27916480Chapman 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 15 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Non-controlled, Multicenter, Multinational Study to Evaluate the Efficacy and Safety of Zemaira® Administration in Chronic Augmentation and Maintenance Therapy in Subjects With Emphysema Due to alpha1-proteinase Inhibitor Deficiency Who Completed Clinical Study CE1226_4001
- ClinicalTrials.gov ID
- NCT00670007
- Acronym / sponsor ID
- CE1226_3001
- Conditions
- Emphysema, Alpha 1-proteinase Inhibitor Deficiency
- Keywords
- Alpha1-proteinase inhibitor deficiency, Chronic augmentation and maintenance therapy, Emphysema, Emphysema due to Alpha 1-proteinase inhibitor deficiency
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- CSL BehringIndustry (pharma, biotech, devices)
- Study start
- Apr 2008
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 1 May 2008 (estimated)
- Results
- Posted 12 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a continuation of the placebo-controlled study CE1226_4001 (NCT00261833) to evaluate the efficacy and safety of Zemaira® intravenous (i.v). administration in subjects with emphysema due to alpha1-proteinase inhibitor deficiency. The long-term verification of a disease-modifying benefit of Zemaira® on the progression of emphysema will be assessed by volume-adjusted lung density, measured yearly by computed tomography (CT).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Zemaira® | Experimental | Biological: Alpha1- proteinase inhibitor [human] |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Subjects who have completed the 2-year treatment and observation period in the Phase 3/4 Zemaira® CE1226_4001 study (NCT00261833) and are willing to sign informed consent
- Males, and non-pregnant, non-lactating females, whose screening pregnancy test is negative and who are using contraceptive methods deemed reliable by the investigator
Key exclusion criteria (8 listed)
- Individuals residing in the US
- Current evidence of alcohol abuse or abuse of 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
- Current tobacco smoker (smoking must be discontinued for at least 6 months prior to study participation)
- Conditions or behaviors that interfere with attending scheduled study visits in the opinion of the investigator
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 inhibitor [human]Also: Zemaira®, Respreeza®Lyophilized preparation of 60 mg/kg body weight intravenously once per week | Biological | Zemaira® |
Primary outcome
Rate of Change of Adjusted Lung Density
Time frame: Up to 2 years
As measured by centralized, standardized computer tomographic (CT) lung densitometry. CT scans were acquired at 2 inspiration states: TLC (Total Lung Capacity; ie, full inspiration) and FRC (Functional Residual Capacity; ie, full expiration). Results were adjusted for total lung volume and are presented as point estimates for the average rate of decline in the early start and delayed start subgroups from a linear random regression model with country, inspiration state (only for 'TLC and FRC state'), time (time elapsed since Day 1 [CE1226_4001]), treatment and treatment by time interaction as fixed effects and subject and subject by time interaction as random coefficients.
10 secondary outcomes
Absolute Change in Adjusted Lung Density
Time frame: From baseline to 2 years
Percent Change in Adjusted Lung Density
Time frame: From baseline to 2 years
Change in Subject-reported Symptoms
Time frame: From baseline to 2 years
Percent Change in Lung Function as Measured by Forced Expiratory Volume in 1 Second (FEV1)
Time frame: From baseline up to 2 years
Percent Change in Lung Function as Measured by Ratio of FEV1/FVC (Forced Vital Capacity)
Time frame: From baseline up to 2 years
Percent Change in Lung Function as Measured by Percent Predicted FEV1
Time frame: From baseline up to 2 years
Number of Subjects With Pulmonary Exacerbations
Time frame: Up to 2 years
Annual Rate in Subject Years of Pulmonary Exacerbations
Time frame: Up to 2 years
Time to First Pulmonary Exacerbation
Time frame: Up to 2 years
Percentage of Subjects With Treatment Emergent Adverse Events
Time frame: From baseline up to 2.5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2016.
- 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 27916480McElvaney NG, Burdon J, Holmes M, Glanville A, Wark PA, Thompson PJ, Hernandez P, Chlumsky J, Teschler H, Ficker JH, Seersholm N, Altraja A, Makitaro R, Chorostowska-Wynimko J, Sanak M, Stoicescu PI, Piitulainen E, Vit O, Wencker M, Tortorici MA, Fries M, Edelman JM, Chapman KR; RAPID Extension Trial Group. Long-term efficacy and safety of alpha1 proteinase inhibitor treatment for emphysema caused by severe alpha1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE). Lancet Respir Med. 2017 Jan;5(1):51-60. doi: 10.1016/S2213-2600(16)30430-1. Epub 2016 Dec 2.
- 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.
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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.
Program Director, Clinical R&D study director
CSL Behring
21 sites in 11 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 [human] in people with Emphysema and Alpha 1-proteinase Inhibitor Deficiency, run by CSL Behring at 21 sites in 11 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 2 inclusion and 8 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 15 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Australia, Canada, Germany, Denmark, Poland and 6 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. 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 12 Jul 2016). 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?
Rate of Change of Adjusted Lung Density (time frame: Up to 2 years). 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 NCT00670007, which also lists 3 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 15 Aug 2016.