Long-term Safety of Alpha1-Proteinase Inhibitor (Human) in Japanese Subjects With Alpha1 Antitrypsin Deficiency (GTI1401-OLE)

A Multi-Center, Open-Label Study to Evaluate the Long-term Safety of Weekly Intravenous Infusions of Alpha1-Proteinase Inhibitor (Human) in Japanese Subjects With Alpha1 Antitrypsin Deficiency

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).

Study Overview

• Status: Completed
• Conditions: Alpha1-Antitrypsin Deficiency
• Intervention / Treatment: Biological: Alpha-1 MP

Detailed Description

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
• Enrollment (Actual): 4
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Aomori, Japan, 036-8563
    • Hiroskai University Hospital
  • Hokkaido, Japan, 060-8648
    • Hokkaido University Hospital
  • Tokyo, Japan, 113-8431
    • Juntendo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who complete participation in Study GTI1401 (i.e., have completed the study through the Week 9 Visit).
• Subjects who will and are able to provide written informed consent.

Exclusion Criteria:

• Subjects with newly diagnosed severe concomitant disease including, but not limited to, congestive heart failure and liver cirrhosis.
• Subjects with newly diagnosed malignant tumor (including malignant melanoma; however, other forms of skin cancer are allowed).
• Female subjects who are 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 or male subjects who have a partner who is of child-bearing potential and is unwilling to practice a highly effective method of contraception throughout the study.
• Subjects with clinical signs and symptoms of active hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) viral infection at the Week 9 Visit of Study GTI1401 and viral infection is further confirmed by testing.
• Subjects with current evidence of smoking or has a positive urine cotinine test at the Week 9 Visit in Study GTI1401 that is due to smoking.
• Subjects who currently participate in a study of another investigational product (other than Alpha-1 MP).
• Subjects who have difficulty in adhering to the protocol or its procedures, in the opinion of the investigator.
• Subjects who have medical conditions that may confound the results of this clinical trial or may endanger these subjects during their participation in this clinical trial in the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alpha-1 MP; Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks.	Biological: Alpha-1 MP; Alpha-1 MP is a stable, sterile, lyophilized preparation of human alpha1-PI, also known as alpha1-antitrypsin.; Other Names: Prolastin-C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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)

Collaborators and Investigators

• Sponsor: Grifols Therapeutics LLC
• Collaborators: Grifols Japan K.K.

Publications and helpful links

General Publications

• Seyama K, Suzuki M, Tasaka S, Nukiwa T, Sato T, Konno S, Sorrells S, Chen J, Aragones ME, Minamino H. Long-term safety of Prolastin(R)-C, an alpha1-proteinase inhibitor, in Japanese patients with alpha1-antitrypsin deficiency. Respir Investig. 2022 Nov;60(6):831-839. doi: 10.1016/j.resinv.2022.07.001. Epub 2022 Aug 12.

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2016
• Primary Completion (Actual): February 16, 2021
• Study Completion (Actual): February 16, 2021

Study Registration Dates

• First Submitted: August 12, 2016
• First Submitted That Met QC Criteria: August 16, 2016
• First Posted (Estimate): August 17, 2016

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Liver Diseases; Genetic Diseases, Inborn; Subcutaneous Emphysema; Emphysema; Alpha 1-Antitrypsin Deficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; Alpha 1-Antitrypsin
• Other Study ID Numbers: GTI1401-OLE; JapicCTI-163194 (Other Identifier: JapicCTI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No