Alpha 1-Antitrypsin Deficiency
Conditions
Keywords
alpha 1-Antitrypsin Deficiency, alpha 1-Antitrypsin, pulmonary emphysema
Brief summary
The purpose of this clinical study (ChAMP - Comparability pharmacokinetics of Alpha-1 Modified Process) is to compare the pharmacokinetic, safety and tolerability of Alpha-1 Proteinase Inhibitor (Human), modified process (Alpha-1 MP) and Prolastin in adult Alpha1-antitrypsin deficient patients. Patients will be infused intravenously with study drug on a weekly schedule for 24 weeks.
Detailed description
The objective of this study is to demonstrate the pharmacokinetic comparability of Alpha-1 MP to Prolastin® in subjects with Alpha1-antitrypsin deficiency. This study is divided into three 8-week treatment sequences including an initial 8-week double-blind treatment period (with one of the 2 study drugs), a second 8-week double-blind treatment period (with the other study drug), and a third 8-week open-label treatment period (with Alpha-1 MP).
Interventions
DRUGAlpha-1 MP
alpha-1 proteinase inhibitor (human), 60 mg/kg body weight
Prolastin
Sponsors
Grifols Therapeutics LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented diagnosis of congenital Alpha1-antitrypsin deficiency * Must be receiving augmentation therapy with plasma-derived (human) Alpha1-Proteinase Inhibitor (Prolastin®) for at least one month prior to study entry. * Signed written informed consent prior to initiation of any study related procedures
Exclusion criteria
* Females who are pregnant, breast feeding, or if of child-bearing potential, unwilling to practice adequate contraception throughout the study * Use of systemic steroids within the 2 weeks prior to receiving study treatment (this does not include the use of inhaled steroids used on a routine or as needed basis). * Subjects who have had exacerbations of their disease within one month of trial entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alpha-1 MP vs. Prolastin® of Area Under the Curve (AUC) From Day 0 to Day 7 | Day 0 to Day 7 | The primary objective of this study was to demonstrate the pharmacokinetic comparability (geometric least square mean ratio of AUC between the Alpha-1 MP vs. Prolastin®, 90% confidence interval falls within 0.80-1.25, FDA Guidance as being bioequivalent between two treatments) of Alpha-1 MP to Prolastin® in subjects with alpha-1-anti-trypsin (AAT) deficiency by comparing AUC from Day 0 to Day 7 of plasma Alpha1-PI measured by the functional activity (potency) assay. AUC from Day 0 to Day 7 was calculated at steady state at the end of the first and second 8-week treatment periods during the 16-week double-blind, crossover phase. |
Countries
United States
Participant flow
Recruitment details
First-subject-first-dose was on 22 May 2006, Last-subject-last-visit was on 28 Feb 2007. The trial was performed at 6 clinical sites in the United States.
Participants by arm
| Arm | Count |
|---|---|
| Alpha-1 MP / Prolastin Sequential, blinded treatment periods of Alpha-1 MP (experimental), then crossed-over to Prolastin (active comparator), followed by open-label Alpha-1 MP | 12 |
| Prolastin / Alpha-1 MP Sequential, blinded treatment periods of Prolastin (active comparator), then crossed-over to Alpha-1 MP (experimental), followed by open-label Alpha-1 MP | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Prolastin / Alpha-1 MP | Alpha-1 MP / Prolastin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 10 Participants | 20 Participants |
| Age, Continuous | 57.0 years STANDARD_DEVIATION 9.33 | 58.4 years STANDARD_DEVIATION 6.86 | 57.7 years STANDARD_DEVIATION 8.04 |
| Region of Enrollment United States | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 24 | 5 / 24 |
| serious Total, serious adverse events | 0 / 24 | 1 / 24 |
Outcome results
Primary
Alpha-1 MP vs. Prolastin® of Area Under the Curve (AUC) From Day 0 to Day 7
The primary objective of this study was to demonstrate the pharmacokinetic comparability (geometric least square mean ratio of AUC between the Alpha-1 MP vs. Prolastin®, 90% confidence interval falls within 0.80-1.25, FDA Guidance as being bioequivalent between two treatments) of Alpha-1 MP to Prolastin® in subjects with alpha-1-anti-trypsin (AAT) deficiency by comparing AUC from Day 0 to Day 7 of plasma Alpha1-PI measured by the functional activity (potency) assay. AUC from Day 0 to Day 7 was calculated at steady state at the end of the first and second 8-week treatment periods during the 16-week double-blind, crossover phase.
Time frame: Day 0 to Day 7
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alpha-1 MP | Alpha-1 MP vs. Prolastin® of Area Under the Curve (AUC) From Day 0 to Day 7 | 155.9 mg*h/mL |
| Prolastin | Alpha-1 MP vs. Prolastin® of Area Under the Curve (AUC) From Day 0 to Day 7 | 152.4 mg*h/mL |
Comparison: To compare AUC 0-7 days between the two treatments (Alpha-1 MP vs. Prolastin),natural log-transformed AUC 0-7 days values were analyzed by analysis of variance (ANOVA).90% CI: [0.97, 1.09]