Alpha₁-Antitrypsin DeficiencyPhase 2/3NCT02282527
A Study to Assess Safety and PK of Liquid Alpha₁-Proteinase Inhibitor (Human) in Treating Alpha₁-Antitrypsin Deficiency
A Phase 2/3 study testing Liquid Alpha₁-PI and Prolastin-C in people with Alpha₁-Antitrypsin Deficiency, run by Grifols Therapeutics LLC at 6 sites in United States.
Trial summary
Grifols Therapeutics Inc. conducted a multi-center, randomized, double-blind, crossover study to evaluate the safety, immunogenicity, and pharmacokinetics (PK) of Liquid Alpha₁-PI compared to the currently licensed product, Prolastin-C, in subjects with Alpha₁-Antitrypsin Deficiency (AATD). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Alpha₁-Antitrypsin Deficiency
- What is being tested?
- Liquid Alpha₁-PI and Prolastin-C
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 6 sitesUnited States
- Study dates
- Oct 2014to Jan 2016
- Phase
- Phase 2/3
- 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, inclusive
- Had a diagnosis of congenital AATD
- Had a documented total alpha₁-PI level < 11 µM. If the total alpha₁-PI level had yet to be documented, a blood draw for total alpha₁-PI level was obtained at the Screening Visit
- Had a post-bronchodilator Forced expiratory volume in 1 second (FEV1) ≥ 30% and < 80% of predicted and FEV1/forced vital capacity (FVC) < 70%
- If the subject had received alpha₁-PI augmentation therapy of any kind, he/she must have been be willing to discontinue that treatment at the Week 1 (Baseline) Visit and remain off any kind of alpha₁-PI treatment, other than the investigational products for this study, while participating in the study
Who cannot join
- Subject had a moderate or severe pulmonary exacerbation during the 4 weeks before the Week 1 (Baseline) Visit
- History of lung or liver transplant
- Any lung surgery during the past 2 years (excluding lung biopsy)
- Liver cirrhosis confirmed by biopsy
- Elevated liver enzymes (aspartate transaminase [AST], alanine aminotransferase [ALT], and alkaline phosphatase [ALP]) equal to or greater than 2.5 times the upper limit of normal
- Severe concomitant disease (e.g., congestive heart failure, clinically significant pulmonary fibrosis, malignant disease [with the exception of skin cancers other than melanoma], history of acute hypersensitivity pneumonitis reaction, or current chronic hypersensitivity pneumonitis)
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- Females who were pregnant, breastfeeding or, if of child-bearing potential, unwilling to practice a highly effective method of contraception (oral, injectable or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or abstinence) throughout the study
- Known previous infection with or clinical signs and symptoms consistent with current hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection
- Smoking during the past 6 months or a positive urine cotinine test at the Screening Visit that is due to smoking
- Participation in another investigational drug study within one month prior to the Week 1 (Baseline) Visit
- History of anaphylaxis or severe systemic response to any plasma-derived alpha1-PI preparation or other blood product(s)
- Use of systemic steroids above a stable dose equivalent to 5 mg/day prednisone (i.e.,10 mg every 2 days) within the 4 weeks prior to the Week 1 (Baseline) Visit inhaled steroids are not considered systemic steroids)
- Use of systemic or aerosolized antibiotics for an exacerbation within the 4 weeks prior to the Week 1 (Baseline) Visit
- Known selective or severe Immunoglobulin A (IgA) deficiency
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
National Jewish Health
Denver, Colorado, 80206
University of Florida Gainesville
Gainesville, Florida, 32610
University of Miami - Miller School of Medicine
Miami, Florida, 33136
Oregon Health and Science University
Portland, Oregon, 97239
University of Texas Health Science Center
Tyler, Texas, 75708
PMG Research of Wilmington
Wilmington, North Carolina, 28401
About this study
Official title: A Multi-center, Randomized, Double-blind, Crossover Study to Assess the Safety and Pharmacokinetics of Liquid Alpha₁-Proteinase Inhibitor (Human) Compared to Prolastin®-C in Subjects With Alpha₁-Antitrypsin Deficiency
Grifols Therapeutics Inc. conducted a multi-center, randomized, double-blind, crossover study to evaluate the safety, immunogenicity, and pharmacokinetics (PK) of Liquid Alpha₁-PI compared to the currently licensed product, Prolastin-C, in subjects with Alpha₁-Antitrypsin Deficiency (AATD).
- Conditions
- Alpha₁-Antitrypsin Deficiency
- Being tested
- Liquid Alpha₁-PI, Prolastin-C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liquid Alpha₁-PIBiological
Liquid Alpha₁-PI, 60 mg/kg, 8 weekly intravenous infusions
Prolastin-CBiological
Prolastin-C, 60 mg/kg, 8 weekly intravenous infusions
| Study group | Role | What they receive |
|---|---|---|
| Treatment Sequence 1 | Other | Subjects were treated first with Liquid Alpha₁-PI and then treated with Prolastin-C Receives: Biological: Liquid Alpha₁-PI; Biological: Prolastin-C |
| Treatment Sequence 2 | Other | Subjects were treated first with Prolastin-C and then treated with Liquid Alpha₁-PI Receives: Biological: Liquid Alpha₁-PI; Biological: Prolastin-C |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC(0-7 Days) Based on Antigenic Content
The primary PK objective of this study was to demonstrate the bioequivalence of Liquid Alpha₁-PI 60 mg/kg to Prolastin-C 60 mg/kg, as measured by AUC from 0 to 7 days (AUC0-7days) using an antigenic content assay of alpha₁-PI, at approximate steady state in subjects with AATD.
Measured: pre-dose, 0, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 8 hours, 1 day, 2 days, 5 days, 7 days post dose
Secondary outcomes (2)
AUC(0-7 Days) Based on Functional Activity
The exploratory PK objective of this study was to demonstrate the bioequivalence of Liquid Alpha₁-PI 60 mg/kg to Prolastin-C 60 mg/kg, as measured by AUC from 0 to 7 days (AUC 0-7 days) using a functional activity assay of alpha₁-PI, at approximate steady state in subjects with AATD.
Measured: pre-dose, 0, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 8 hours, 1 day, 2 days, 5 days, 7 days post dose
Number of Subjects With Immunogenicity Response
Blood samples for immunogenicity testing were collected at Weeks 1 (Baseline), 9, 17, and 20. Any samples that tested positive for alpha₁-PI antibodies were tested for neutralizing antibodies and antibody titer. Immunogenicity testing was performed using validated assays in a multitiered approach. Samples collected at Week 1 (Baseline) and at Weeks 9 and 20 were tested for immunogenicity while samples collected at Week 17 were to be tested for immunogenicity only if deemed appropriate (eg, unexpected PK profile).
Measured: Weeks 1, 9, 17, and 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2014 (estimated)
- Study startOct 2014
- Primary completionJan 2016
- Study completionJan 2016
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.
- Other trials for Alpha₁-Antitrypsin DeficiencyStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grifols Therapeutics LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02282527
- Sponsor's protocol ID
- GTI1402
- Status last verified
- Jan 2017
- First submitted
- 31 Oct 2014
- Last updated
- 13 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Randomized, Double-blind, Crossover Study to Assess the Safety and Pharmacokinetics of Liquid Alpha₁-Proteinase Inhibitor (Human) Compared to Prolastin®-C in Subjects With Alpha₁-Antitrypsin Deficiency
- ClinicalTrials.gov ID
- NCT02282527
- Acronym / sponsor ID
- GTI1402
- Conditions
- Alpha₁-Antitrypsin Deficiency
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Grifols Therapeutics LLCIndustry (pharma, biotech, devices)
- Study start
- Oct 2014
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 4 Nov 2014 (estimated)
- Results
- Posted 13 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Grifols Therapeutics Inc. conducted a multi-center, randomized, double-blind, crossover study to evaluate the safety, immunogenicity, and pharmacokinetics (PK) of Liquid Alpha₁-PI compared to the currently licensed product, Prolastin-C, in subjects with Alpha₁-Antitrypsin Deficiency (AATD).
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 |
|---|---|---|
| Treatment Sequence 1 | Other | Biological: Liquid Alpha₁-PI, Biological: Prolastin-CSubjects were treated first with Liquid Alpha₁-PI and then treated with Prolastin-C |
| Treatment Sequence 2 | Other | Biological: Liquid Alpha₁-PI, Biological: Prolastin-CSubjects were treated first with Prolastin-C and then treated with Liquid Alpha₁-PI |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Be between 18 and 70 years of age, inclusive
- Had a diagnosis of congenital AATD
- Had a documented total alpha₁-PI level < 11 µM. If the total alpha₁-PI level had yet to be documented, a blood draw for total alpha₁-PI level was obtained at the Screening Visit
- Had a post-bronchodilator Forced expiratory volume in 1 second (FEV1) ≥ 30% and < 80% of predicted and FEV1/forced vital capacity (FVC) < 70%
- If the subject had received alpha₁-PI augmentation therapy of any kind, he/she must have been be willing to discontinue that treatment at the Week 1 (Baseline) Visit and remain off any kind of alpha₁-PI treatment, other than the investigational products for this study, while participating in the study
Key exclusion criteria (14 listed)
- Subject had a moderate or severe pulmonary exacerbation during the 4 weeks before the Week 1 (Baseline) Visit
- History of lung or liver transplant
- Any lung surgery during the past 2 years (excluding lung biopsy)
- Liver cirrhosis confirmed by biopsy
- Elevated liver enzymes (aspartate transaminase [AST], alanine aminotransferase [ALT], and alkaline phosphatase [ALP]) equal to or greater than 2.5 times the upper limit of normal
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 |
|---|---|---|
| Liquid Alpha₁-PILiquid Alpha₁-PI, 60 mg/kg, 8 weekly intravenous infusions | Biological | Treatment Sequence 1, Treatment Sequence 2 |
| Prolastin-CProlastin-C, 60 mg/kg, 8 weekly intravenous infusions | Biological | Treatment Sequence 1, Treatment Sequence 2 |
Primary outcome
AUC(0-7 Days) Based on Antigenic Content
Time frame: pre-dose, 0, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 8 hours, 1 day, 2 days, 5 days, 7 days post dose
The primary PK objective of this study was to demonstrate the bioequivalence of Liquid Alpha₁-PI 60 mg/kg to Prolastin-C 60 mg/kg, as measured by AUC from 0 to 7 days (AUC0-7days) using an antigenic content assay of alpha₁-PI, at approximate steady state in subjects with AATD.
2 secondary outcomes
AUC(0-7 Days) Based on Functional Activity
Time frame: pre-dose, 0, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 8 hours, 1 day, 2 days, 5 days, 7 days post dose
Number of Subjects With Immunogenicity Response
Time frame: Weeks 1, 9, 17, and 20
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Liquid Alpha₁-PI and Prolastin-C in people with Alpha₁-Antitrypsin Deficiency, run by Grifols Therapeutics LLC at 6 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 5 inclusion and 14 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 13 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 13 Mar 2017). 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?
AUC(0-7 Days) Based on Antigenic Content (time frame: pre-dose, 0, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 8 hours, 1 day, 2 days, 5 days, 7 days post dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Mar 2017.