Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Alpha1-Proteinase Inhibitor (Human), Alpha-1 MP, Prolastin, Liquid Alpha1-Proteinase Inhibitor (Human), alpha1-antitrypsin
Alpha1-Proteinase Inhibitor · 9 trials · 6 indications
Monitoring of AEs
Monitoring of SAEs
Monitoring of discontinuations due to AEs
Whole lung PD15 measured by CT scan
An adverse event is any untoward medical occurrence in a subject or clinical investigation subject administered with a pharmaceutical product. The adverse event does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the medicinal product.
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.
An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether considered related to the medicinal product. TEAEs were defined as any AE occurring after or on the first Alpha-1 MP infusion until the final visit of study.
ADRs were defined as adverse events (AEs) which were in the investigator's opinion of causal relationship to the study treatment. AE was defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product.
A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether considered related to the medicinal product. TEAEs were defined as any AE occurring after or on the first Alpha-1 MP infusion until the final visit of study. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
COPD exacerbation was defined as an increase in respiratory symptoms (dyspnea, increased cough, and/or production of sputum) over baseline that usually requires medical intervention.
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a medicinal product or study treatment and which did not necessarily have a causal relationship with this administration. An AE was considered serious in any of the following outcomes or deemed significant for any other reason: death; life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly/birth defect.
Vital signs included analysis of heart rate, blood pressure, respiratory rate, and temperature. Clinically significant findings in vital signs were based on investigator's discretion.
Clinical laboratory parameters included analysis of hematology, blood chemistry, and urinalysis. Clinically significant findings in clinical laboratory parameters were based on investigator's discretion.
Pulmonary function tests were measured by spirometry. It included Forced Expired Volume in 1 second (FEV1), Forced Vital Capacity (FVC), which were performed according to American Thoracic Society/ European Respiratory Society (ATS/ERS) guidelines. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. PFTs were performed before infusion both pre- and post-bronchodilator administration. The post-bronchodilator PFT was performed 15 to 30 minutes after bronchodilator administration. The same bronchodilator was used throughout the study. Clinically significant findings in pulmonary function tests were based on investigator's discretion.
Alpha1-PI level was measured by nephelometry.
| Arm | Type | Description |
|---|---|---|
| Alpha-1 MP | EXPERIMENTAL | Alpha-1 MP 60 mg/kg/week for up to 104 weeks |
| Alpha-1 MP 60 mg/kg | EXPERIMENTAL | Alpha-1 MP 60 mg/kg administered weekly by IV infusion for 156 weeks |
| Alpha-1 MP 120 mg/kg | EXPERIMENTAL | Alpha-1 MP 120 mg/kg administered weekly by IV infusion for 156 weeks |
| Placebo | PLACEBO_COMPARATOR | 0.9% Sodium Chloride for Injection, USP, administered weekly by IV infusion for 156 weeks |
| Alpha-1 Proteinase Inhibitor (Human), modified process | EXPERIMENTAL | Study the safety and tolerability of weekly infusions of Alpha-1 Proteinase Inhibitor (Human), modified process (Alpha-1 MP, 60 mg/kg) over 20 weeks of therapy in adult Alpha-1 antitrypsin deficient subjects. |
| 1 Alpha-1 MP | EXPERIMENTAL | Sequential, blinded treatment periods of Alpha-1 MP (experimental), then crossed-over to Prolastin (active comparator), followed by open-label Alpha-1 MP |
| 2 Prolastin | ACTIVE_COMPARATOR | Sequential, blinded treatment periods of Prolastin (active comparator), then crossed-over to Alpha-1 MP (experimental), followed by open-label Alpha-1 MP |
| Prolastin 120 mg/kg + Standard Medical Treatment | EXPERIMENTAL | Subjects will receive Prolastin, two intravenous infusion (IV) doses of 120 milligram per kilogram (mg/kg), based upon the subject's body weight, on Day 1 and Day 8. Subjects will also receive all standard of care interventions while hospitalized, from Day 1 to Day 29. |
| Standard Medical Treatment | ACTIVE_COMPARATOR | Subjects will receive all standard of care interventions while hospitalized, from Day 1 to Day 29. |
| Group 1 | EXPERIMENTAL | Prolastin |
| Group 2 | PLACEBO_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| Alpha-1 MP | BIOLOGICAL | Alpha-1 MP 60 mg/kg/week for up to 104 weeks |
| 0.9% Sodium Chloride for Injection, USP | OTHER | - |
| alpha-1 proteinase inhibitor (human) | DRUG | 60 mg/kg weekly for 20 weeks |
| Prolastin | BIOLOGICAL | Intravenous infusion 120 mg/kg |
| Standard Medical Treatment | DRUG | Standard medical treatment per local policies or guidelines |
| Alpha1-Proteinase Inhibitor (Human) | DRUG | Weekly infusion of 60 mg/kg body weight for 2 years |
| Albumin (Human) 20%, United States Pharmacopeia (USP) | DRUG | Weekly infusion for 2 years. Albumin (Human) 20% will be diluted with 5% glucose to a final concentration of 2.0%. |
Inclusion Criteria: * Has completed participation in Study GTi1201 (ie, completed Week 156 and Week 160/End-of-Study Visit) OR has experienced a decline in FEV1 at the annualized rate of ≥134.4 mL/year at or after the Week 104 Visit in GTi1201. * Is willing and able to provide informed consent Exc...
Alpha1-Proteinase Inhibitor is being studied for Alpha 1-Antitrypsin Deficiency and Cystic Fibrosis. It is a rare disease therapy developed by Grifols, S.A. The clinical program includes trials in patients with AAT deficiency and in cystic fibrosis patients, with the goal of addressing the underlying protein deficiency.
Alpha1-Proteinase Inhibitor is developed by Grifols, S.A., which trades under the ticker GRFS. Grifols is the sponsor of the clinical trials evaluating this therapy in Alpha 1-Antitrypsin Deficiency and Cystic Fibrosis.
Alpha1-Proteinase Inhibitor is in Phase 3 development. A Phase 3 trial, NCT00301366, evaluated the safety and tolerability of Alpha-1 Modified Process in subjects with Alpha-1-antitrypsin deficiency. The program also includes completed Phase 2 trials. It is investigational and has not been approved by the FDA.
Alpha1-Proteinase Inhibitor has been studied in completed trials including NCT00301366, a Phase 3 safety and tolerability study in Alpha-1-antitrypsin deficiency, NCT00486837, a Phase 2 study of inhaled Prolastin in cystic fibrosis patients, and NCT00263887, a Phase 2 trial in AAT-deficient patients with emphysema.
Yes. Alpha1-Proteinase Inhibitor is also known as Alpha1-Proteinase Inhibitor (Human), alpha-1 proteinase inhibitor (human), and alpha-1 proteinase inhibitor. These names refer to the same Grifols therapy being studied in Alpha 1-Antitrypsin Deficiency and Cystic Fibrosis.