Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Alpha-1 MP · 5 trials · 4 indications
Monitoring of AEs
Monitoring of SAEs
Monitoring of discontinuations due to AEs
Whole lung PD15 measured by CT scan
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 |
| 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 |
| 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 | Prolastin |
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...
Alpha-1 MP is an investigational therapy for Alpha-1 Antitrypsin Deficiency, including pulmonary emphysema associated with the condition. It is being developed as a treatment for patients with this rare genetic disorder that can lead to lung damage.
Alpha-1 MP targets SERPINA1, the gene that encodes alpha-1 antitrypsin protein. The therapy is designed to address the deficiency of this protein, which plays a role in protecting lung tissue from damage.
Alpha-1 MP is being developed by Grifols, S.A., a biopharmaceutical company. Grifols is publicly traded under the ticker symbol GRFS.
Alpha-1 MP is in Phase 3 clinical development. It is an investigational drug and has not been approved by regulatory authorities. The Phase 3 trials are evaluating its efficacy and safety in patients with pulmonary emphysema due to Alpha-1 Antitrypsin Deficiency.
Alpha-1 MP is being studied in several clinical trials, including NCT02796937, a Phase 3 long-term safety study in patients with pulmonary emphysema due to Alpha-1 Antitrypsin Deficiency, and NCT01983241, a Phase 3 efficacy and safety trial. Earlier Phase 1 trials include NCT02870348 and NCT02870309.
Alpha-1 MP is a modified process version of alpha1-proteinase inhibitor (human). It is designed to provide the same therapeutic protein but through an improved manufacturing process, as indicated in the clinical trial titles.