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

NCT02870348 | Completed Phase 1 Results

• 2 other identifiers: GTI1401-OLEJapicCTI-163194
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 3

Brief Summary

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).

Conditions

Alpha1-Antitrypsin Deficiency

Outcome Measures

Primary Outcomes (9)

• 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)

Study Arms (1)

Alpha-1 MP

EXPERIMENTAL

Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks.

Biological: Alpha-1 MP

Interventions

Alpha-1 MP BIOLOGICAL

Alpha-1 MP is a stable, sterile, lyophilized preparation of human alpha1-PI, also known as alpha1-antitrypsin.

Also known as: Prolastin-C

Alpha-1 MP

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Grifols Therapeutics LLC: lead
• Grifols Japan K.K.: collaborator

Study Sites (3)

Hiroskai University Hospital

Aomori, 036-8563, Japan

Location

Hokkaido University Hospital

Hokkaido, 060-8648, Japan

Location

Juntendo University Hospital

Tokyo, 113-8431, Japan

Location

Related Publications (1)

• 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.

  PMID: 35970714 DERIVED

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Interventions

Mp alpha1 receptor

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Sandra Camprubi
• Organization: Instituto Grifols SA

sandra.camprubi@grifols.com

+34935710049

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2016
• First Posted: August 17, 2016
• Study Start: July 29, 2016
• Primary Completion: February 16, 2021
• Study Completion: February 16, 2021
• Last Updated: March 31, 2022
• Results First Posted: March 21, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

JP (3)