EmphysemaPhase 2SPARKNCT01213043
Safety and Pharmacokinetics of Alpha-1 Proteinase Inhibitor in Subjects With Alpha1-Antitrypsin Deficiency
A Phase 2 study testing Prolastin-C, 60 mg/kg and Prolastin-C, 120 mg/kg in people with Emphysema and Alpha 1-antitrypsin Deficiency (AATD), run by Grifols Therapeutics LLC at 5 sites in United States.
Trial summary
This is a study to assess the safety and pharmacokinetics of weekly infusions of 120 mg/kg of Prolastin-C (alpha1-proteinase inhibitor [alpha1-PI] [Human]), compared to weekly infusions of 60 mg/kg of Prolastin-C in patients with alpha 1-antitrypsin deficiency (AATD). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Emphysema, Alpha 1-antitrypsin Deficiency (AATD)
- What is being tested?
- Prolastin-C, 60 mg/kg and Prolastin-C, 120 mg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 5 sitesUnited States
- Study dates
- Nov 2010to Jan 2012
- Phase
- Phase 2
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be between 18 and 70 years of age
- Have a documented diagnosis of congenital AATD
- Have a post-bronchodilator Forced Expired Volume in 1 second (FEV1) of ≥30% and <80% and FEV1/forced vital capacity (FVC) <70%
- If receiving alpha-1 PI augmentation therapy, be willing to discontinue the treatment for the duration of the study
Who cannot join
- Had a moderate or severe pulmonary exacerbation during the 4 weeks before the study
- History of lung or liver transplant
- Any lung surgery during the past 2 years
- Confirmed liver cirrhosis
- Elevated liver enzymes
- Severe concurrent disease
Show all 11Show fewer
- Females who are pregnant or breast-feeding or unwilling to practice effective contraception during the study
- Infection with hepatitis A, B, or C, human immunodeficiency or parvovirus B19
- Smoking during the past 6 months
- Use of systemic steroids within 4 weeks of the study
- Use of antibiotics for an exacerbation within 4 weeks of the study
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Medical University of South Carolina, Division of Pulmonary and Critical Care Medicine
Charleston, South Carolina, 29425-6300
University of Florida College of Medicine
Gainesville, Florida, 32610-0225
University of Miami
Miami, Florida, 33136
Temple University Hosptial/Temple Lung Center
Philadelphia, Pennsylvania, 19140
The University of Texas Health Science Center at Tyler
Tyler, Texas, 75708
About this study
Official title: A Randomized Double-blind Crossover Study to Assess the Safety and Pharmacokinetics of Two Different Doses of Weekly Intravenous Administration of Alpha1-Proteinase Inhibitor (Human) Prolastin®-C in Subjects With Alpha1-Antitrypsin Deficiency
This is a study to assess the safety and pharmacokinetics of weekly infusions of 120 mg/kg of Prolastin-C (alpha1-proteinase inhibitor [alpha1-PI] [Human]), compared to weekly infusions of 60 mg/kg of Prolastin-C in patients with alpha 1-antitrypsin deficiency (AATD).
Read the detailed description
The question of whether higher doses of alpha1-PI (>60 mg/kg) are able to provide better protection to patients with alpha 1-antitrypsin deficiency is currently unknown. As a first step to address this question, the present study has been undertaken. This is a multi-center, randomized, double-blind, crossover study to assess the safety and pharmacokinetics of weekly infusions of 120 mg/kg of Prolastin-C, compared to weekly infusions of 60 mg/kg of Prolastin-C in patients with alpha 1-antitrypsin deficiency. This study is a crossover design with 2 treatment sequences:
Treatment Sequence 1: 60 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 120 mg/kg weekly infusion of Prolastin-C for 8 weeks (starting at Week 1) (total of 16 treatment weeks)
Treatment Sequence 2: 120 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 60 mg/kg weekly infusion of Prolastin-C for 8 weeks (starting at Week 11) (total of 16 treatment weeks)
Approximately 15 subjects are planned to be entered into each treatment sequence.
At Weeks 8 to 11 and Weeks 18 to 21, a total of 15 serial blood samples for each subject will be drawn for pharmacokinetic analysis. The expected duration of the study subject's participation will be approximately 25 weeks (which includes a 3-Week Screening Phase, 2-Week Washout Period [between different alpha-1 PI treatment doses], and a 4-Week Follow-up Period). The following safety parameters will be assessed: adverse events, pulmonary exacerbations, vital signs, pulmonary function tests, and clinical laboratory tests.
- Conditions
- Emphysema, Alpha 1-antitrypsin Deficiency (AATD)
- Being tested
- Prolastin-C, 60 mg/kg, Prolastin-C, 120 mg/kg
- Keywords
- emphysema, alpha 1-antitrypsin, alpha 1-antitrypsin deficiency (AATD), alpha 1-proteinase inhibitor (Alpha-1 PI)
- 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.
Prolastin-C, 60 mg/kgBiological
Also called Alpha1-Proteinase Inhibitor, Alpha1-Proteinase Inhibitor (Human), Modified Process, Alpha-1 MP
60 mg/kg weekly infusion of Prolastin-C for 8 weeks
Prolastin-C, 120 mg/kgBiological
Also called Alpha1-Proteinase Inhibitor, Alpha1-Proteinase Inhibitor (Human), Modified Process, Alpha-1 MP
120 mg/kg weekly infusion of Prolastin-C for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Prolastin-C, 60 mg/kg | Active comparator | 60 mg/kg weekly infusion of Prolastin-C for 8 weeks. Subjects were infused with 60 mg/kg Prolastin-C by means of one of two possible treatment sequences: 1) 60 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 120 mg/kg Prolastin-C for 8 weeks, or 2) 120 mg/kg Prolastin-C for 8 weeks followed by 60 mg/kg weekly infusion of Prolastin-C for 8 weeks (total of 16 weeks). Receives: Biological: Prolastin-C, 60 mg/kg |
| Prolastin-C, 120 mg/kg | Experimental | 120 mg/kg weekly infusion of Prolastin-C for 8 weeks. Subjects were infused with 120 mg/kg Prolastin-C by means of one of two possible treatment sequences: 1) 60 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 120 mg/kg Prolastin-C for 8 weeks, or 2) 120 mg/kg Prolastin-C for 8 weeks followed by 60 mg/kg weekly infusion of Prolastin-C for 8 weeks (total of 16 weeks). Receives: Biological: Prolastin-C, 120 mg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Subjects With Treatment-Emergent Adverse Events (TEAEs)
Number of subjects experiencing at least one TEAE. TEAEs were defined as any adverse event (AE) during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).
Measured: 22 weeks
Subjects With Drug-Related TEAE(s)
Number of subjects with at least one TEAE that was determined by the Investigator to be either "possibly related" or "related" to the investigational product (i.e., Prolastin-C).
Measured: 22 weeks
Subjects With Treatment-Emergent Serious Adverse Events (SAEs)
Number of subjects who experienced at least one treatment-emergent SAE.
Measured: 22 weeks
Subjects Withdrawn Due to an AE(s)
Number of subjects who were withdrawn from the study due to at least one AE.
Measured: 22 weeks
Subjects With Treatment-Emergent Pulmonary Exacerbation(s)
Number of subjects with at least one treatment-emergent pulmonary exacerbation
Measured: 22 weeks
Subjects With Severe TEAE(s) or Pulmonary Exacerbation(s)
Number of subjects who experienced at least one severe TEAE or pulmonary exacerbation.
Measured: 22 weeks
Number of TEAEs
Total number of TEAEs reported.
Measured: 22 Weeks
Number of Drug-related TEAEs
Total number of drug-related TEAEs reported
Measured: 22 Weeks
Number of Treatment-Emergent Pulmonary Exacerbations
Total number of treatment-emergent pulmonary exacerbations.
Measured: 22 Weeks
Secondary outcomes (2)
AUC0-7days
Area Under the Alpha-1 PI Concentration-Time Curve from Day 0 to Day 7
Measured: Week 8 and Week 18 at the following timepoints: 0 (pre-infusion), completion of first infusion bag, completion of 2nd infusion bag, and 15 min, 30 min, and 1, 2, 4, 8, 24, 48, 120, and 168 hours post-dose
Mean Trough
The average trough concentration at steady-state, calculated as the mean value using the four Trough measurements obtained at Weeks 6, 7, 8 and at 7 days (168 hours) post infusion at Week 8 for the first treatment period or prior to the start of the infusions at Weeks 16, 17, 18, and at 7 days (168 hours) post infusion at Week 18 for the second treatment period.
Measured: Single measurment immediately prior to infusion at Weeks 6, 7, 8, 9 and Weeks 16, 17, 18, 19
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2010 (estimated)
- Study startNov 2010
- Primary completionJan 2012
- Study completionJan 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 (1)Papers the sponsor has linked to this study.
- Other trials for EmphysemaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grifols Therapeutics LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mark Brantly, MD, Principal investigator, University of FloridaMichael Campos, MD, Principal investigator, University of MiamiFriedrich Kueppers, MD, Principal investigator, Temple University Hospital/Temple Lung CenterJames Stocks, MD, Principal investigator, The University of Texas Health Science Center at TylerCharlie Strange, MD, Principal investigator, Medical University of South Carolina, Division of Pulmonary and Critical Care Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01213043
- Sponsor's protocol ID
- T6004-201/Version 2
- Acronym
- SPARK
- Status last verified
- Apr 2013
- First submitted
- 29 Sep 2010
- Last updated
- 20 May 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Willis T, Wee K, Mohn G. A high-purity Alpha-1 proteinase inhibitor from human plasma, TAL6004. Proceeding of the 19th European Respiratory Society Annual Congress; 2009 Sep 12-16; Vienna, Austria. Abstracts;34:S53.
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double-blind Crossover Study to Assess the Safety and Pharmacokinetics of Two Different Doses of Weekly Intravenous Administration of Alpha1-Proteinase Inhibitor (Human) Prolastin®-C in Subjects With Alpha1-Antitrypsin Deficiency
- ClinicalTrials.gov ID
- NCT01213043
- Acronym / sponsor ID
- SPARK / T6004-201/Version 2
- Conditions
- Emphysema, Alpha 1-antitrypsin Deficiency (AATD)
- Keywords
- emphysema, alpha 1-antitrypsin, alpha 1-antitrypsin deficiency (AATD), alpha 1-proteinase inhibitor (Alpha-1 PI)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Grifols Therapeutics LLCIndustry (pharma, biotech, devices)
- Study start
- Nov 2010
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 1 Oct 2010 (estimated)
- Results
- Posted 20 May 2013
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 study to assess the safety and pharmacokinetics of weekly infusions of 120 mg/kg of Prolastin-C (alpha1-proteinase inhibitor [alpha1-PI] [Human]), compared to weekly infusions of 60 mg/kg of Prolastin-C in patients with alpha 1-antitrypsin deficiency (AATD).
Detailed description
The question of whether higher doses of alpha1-PI (>60 mg/kg) are able to provide better protection to patients with alpha 1-antitrypsin deficiency is currently unknown. As a first step to address this question, the present study has been undertaken. This is a multi-center, randomized, double-blind, crossover study to assess the safety and pharmacokinetics of weekly infusions of 120 mg/kg of Prolastin-C, compared to weekly infusions of 60 mg/kg of Prolastin-C in patients with alpha 1-antitrypsin deficiency. This study is a crossover design with 2 treatment sequences:
Treatment Sequence 1: 60 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 120 mg/kg weekly infusion of Prolastin-C for 8 weeks (starting at Week 1) (total of 16 treatment weeks)
Treatment Sequence 2: 120 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 60 mg/kg weekly infusion of Prolastin-C for 8 weeks (starting at Week 11) (total of 16 treatment weeks)
Approximately 15 subjects are planned to be entered into each treatment sequence.
At Weeks 8 to 11 and Weeks 18 to 21, a total of 15 serial blood samples for each subject will be drawn for pharmacokinetic analysis. The expected duration of the study subject's participation will be approximately 25 weeks (which includes a 3-Week Screening Phase, 2-Week Washout Period [between different alpha-1 PI treatment doses], and a 4-Week Follow-up Period). The following safety parameters will be assessed: adverse events, pulmonary exacerbations, vital signs, pulmonary function tests, and clinical laboratory tests.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prolastin-C, 60 mg/kg | Active comparator | Biological: Prolastin-C, 60 mg/kg60 mg/kg weekly infusion of Prolastin-C for 8 weeks. Subjects were infused with 60 mg/kg Prolastin-C by means of one of two possible treatment sequences: 1) 60 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 120 mg/kg Prolastin-C for 8 weeks, or 2) 120 mg/kg Prolastin-C for 8 weeks followed by 60 mg/kg weekly infusion of Prolastin-C for 8 weeks (total of 16 weeks). |
| Prolastin-C, 120 mg/kg | Experimental | Biological: Prolastin-C, 120 mg/kg120 mg/kg weekly infusion of Prolastin-C for 8 weeks. Subjects were infused with 120 mg/kg Prolastin-C by means of one of two possible treatment sequences: 1) 60 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 120 mg/kg Prolastin-C for 8 weeks, or 2) 120 mg/kg Prolastin-C for 8 weeks followed by 60 mg/kg weekly infusion of Prolastin-C for 8 weeks (total of 16 weeks). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Be between 18 and 70 years of age
- Have a documented diagnosis of congenital AATD
- Have a post-bronchodilator Forced Expired Volume in 1 second (FEV1) of ≥30% and <80% and FEV1/forced vital capacity (FVC) <70%
- If receiving alpha-1 PI augmentation therapy, be willing to discontinue the treatment for the duration of the study
Key exclusion criteria (11 listed)
- Had a moderate or severe pulmonary exacerbation during the 4 weeks before the study
- History of lung or liver transplant
- Any lung surgery during the past 2 years
- Confirmed liver cirrhosis
- Elevated liver enzymes
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 |
|---|---|---|
| Prolastin-C, 60 mg/kgAlso: Alpha1-Proteinase Inhibitor, Alpha1-Proteinase Inhibitor (Human), Modified Process, Alpha-1 MP60 mg/kg weekly infusion of Prolastin-C for 8 weeks | Biological | Prolastin-C, 60 mg/kg |
| Prolastin-C, 120 mg/kgAlso: Alpha1-Proteinase Inhibitor, Alpha1-Proteinase Inhibitor (Human), Modified Process, Alpha-1 MP120 mg/kg weekly infusion of Prolastin-C for 8 weeks | Biological | Prolastin-C, 120 mg/kg |
Primary outcome
Subjects With Treatment-Emergent Adverse Events (TEAEs)
Time frame: 22 weeks
Number of subjects experiencing at least one TEAE. TEAEs were defined as any adverse event (AE) during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).
Subjects With Drug-Related TEAE(s)
Time frame: 22 weeks
Number of subjects with at least one TEAE that was determined by the Investigator to be either "possibly related" or "related" to the investigational product (i.e., Prolastin-C).
Subjects With Treatment-Emergent Serious Adverse Events (SAEs)
Time frame: 22 weeks
Number of subjects who experienced at least one treatment-emergent SAE.
Subjects Withdrawn Due to an AE(s)
Time frame: 22 weeks
Number of subjects who were withdrawn from the study due to at least one AE.
Subjects With Treatment-Emergent Pulmonary Exacerbation(s)
Time frame: 22 weeks
Number of subjects with at least one treatment-emergent pulmonary exacerbation
Subjects With Severe TEAE(s) or Pulmonary Exacerbation(s)
Time frame: 22 weeks
Number of subjects who experienced at least one severe TEAE or pulmonary exacerbation.
Number of TEAEs
Time frame: 22 Weeks
Total number of TEAEs reported.
Number of Drug-related TEAEs
Time frame: 22 Weeks
Total number of drug-related TEAEs reported
Number of Treatment-Emergent Pulmonary Exacerbations
Time frame: 22 Weeks
Total number of treatment-emergent pulmonary exacerbations.
2 secondary outcomes
AUC0-7days
Time frame: Week 8 and Week 18 at the following timepoints: 0 (pre-infusion), completion of first infusion bag, completion of 2nd infusion bag, and 15 min, 30 min, and 1, 2, 4, 8, 24, 48, 120, and 168 hours post-dose
Mean Trough
Time frame: Single measurment immediately prior to infusion at Weeks 6, 7, 8, 9 and Weeks 16, 17, 18, 19
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundWillis T, Wee K, Mohn G. A high-purity Alpha-1 proteinase inhibitor from human plasma, TAL6004. Proceeding of the 19th European Respiratory Society Annual Congress; 2009 Sep 12-16; Vienna, Austria. Abstracts;34:S53.
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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.
Mark Brantly, MD principal investigator
University of Florida
Michael Campos, MD principal investigator
University of Miami
Friedrich Kueppers, MD principal investigator
Temple University Hospital/Temple Lung Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Prolastin-C, 60 mg/kg and Prolastin-C, 120 mg/kg in people with Emphysema and Alpha 1-antitrypsin Deficiency (AATD), run by Grifols Therapeutics LLC at 5 sites in United States.
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 4 inclusion and 11 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 20 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 20 May 2013). 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?
Subjects With Treatment-Emergent Adverse Events (TEAEs) (time frame: 22 weeks). The study lists 9 primary outcomes in all. 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 NCT01213043, which also lists 1 linked publication.
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 20 May 2013.