This is a multi-center, open-label study to evaluate the long-term safety of weekly intravenous (IV) infusions of 60 mg/kg alpha1-PI (human), modified process (Alpha-1 MP) in adult participants with Alpha1 Antitrypsin Deficiency (AATD) in Japan who have completed Study GTI1401 (NCT02870309).
This is a multi-center, open-label study to evaluate the long-term safety of weekly IV infusions of 60 mg/kg Alpha-1 MP in adult participants with AATD in Japan who have completed Study GTI1401. Study GTI1401 is being conducted to evaluate the safety and pharmacokinetics (PK) of Alpha-1 MP in participants with AATD in Japan. In the current study, GTI1401-OLE, participants will be administered 60 mg/kg Alpha-1 MP by weekly IV infusion for approximately 1 year (can be renewed annually with the consent of the participants unless the sponsor informs of discontinuation of this OLE trial) to assess the long-term safety of Alpha-1 MP in participants with AATD. This study will be conducted at up to 5 centers in Japan. At the Week 9 Visit of Study GTI1401, after giving consent, on the same day, participants will be assessed for eligibility at Screening/Extension (Ext) Week 1 Visit for this extension study, Study GTI1401-OLE. If eligible, participants will be administered weekly IV infusions of 60 mg/kg Alpha-1 MP for approximately 1 year or longer. The Week 9 Visit of GTI1401 will be the End of Study Visit for the participants who are enrolled in Study GTI1401-OLE. Participants in Study GTI1401-OLE will have the option to remain in Study GTI1401-OLE and continue to receive weekly IV infusions of 60 mg/kg Alpha-1 MP for another year or longer. If participants plan to conclude their participation in the study (GTI1401-OLE) early (before Ext. Week 52), participants will be asked to complete the End of Study Follow-Up Assessments, which will be scheduled 4 weeks after the last infusion.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
4
Alpha-1 MP is a stable, sterile, lyophilized preparation of human alpha1-PI, also known as alpha1-antitrypsin.
Hiroskai University Hospital
Aomori, Japan
Hokkaido University Hospital
Hokkaido, Japan
Juntendo University Hospital
Tokyo, Japan
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (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. TEAEs were defined as any AE occurring after or on the first Alpha-1 MP infusion until the final visit of study.
Time frame: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Number of Participants With Adverse Drug Reaction (ADRs)
ADRs were defined as all noxious and unintended responses to a medicinal product or study treatment related to any dose. 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.
Time frame: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Number of Participants With Serious Adverse Events (SAEs)
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.
Time frame: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Number of Participants With Discontinuations Due to Adverse Events (AEs) or Serious Adverse Events (SAEs)
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.
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Time frame: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Number of Participants With Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
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.
Time frame: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Number of Participants With Clinically Significant Findings in Vital Signs
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.
Time frame: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Number of Participants With Clinically Significant Findings in Clinical Laboratory Parameters
Clinical laboratory parameters included analysis of hematology, blood chemistry, and urinalysis. Clinically significant findings in clinical laboratory parameters were based on investigator's discretion.
Time frame: Extension (Ext) Weeks 26, 52, 78, 104, 130, 156,182, 208 (prior to study drug administration) until end of study (Up to 228 weeks)
Number of Participants With Clinically Significant Findings in Pulmonary Function Tests (PFTs)
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.
Time frame: Extension (Ext) Weeks 26, 52, 78, 104, 130, 156,182, 208 (prior to study drug administration) until end of study (Up to 228 weeks)
Trough Levels of Alpha1- Proteinase Inhibitor
Alpha1-PI level was measured by nephelometry.
Time frame: Extension (Ext) Weeks 12, 24, 36, 48, 64, 76, 88, 100, 116, 128, 140, 152, 168, 180, 192, 204 (prior to study drug administration) until end of study (Up to 228 weeks)