Clinical trial NCT02870348: Long-term Safety of Alpha1-Proteinase Inhibitor (Human) in Japanese Subjects With Alpha1 Antitrypsin Deficiency (GTI1401-OLE)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Alpha1-Antitrypsin Deficiency
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
Collaborators: name: Grifols Japan K.K.
First posted: 2016-08-17
Enrollment: 4
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
measure: Number of Participants With Adverse Drug Reaction (ADRs)
timeFrame: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
measure: Number of Participants With Discontinuations Due to Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
measure: Number of Participants With Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
timeFrame: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
measure: Number of Participants With Clinically Significant Findings in Vital Signs
timeFrame: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
measure: Number of Participants With Clinically Significant Findings in Clinical Laboratory Parameters
timeFrame: Extension (Ext) Weeks 26, 52, 78, 104, 130, 156,182, 208 (prior to study drug administration) until end of study (Up to 228 weeks)
measure: Number of Participants With Clinically Significant Findings in Pulmonary Function Tests (PFTs)
timeFrame: Extension (Ext) Weeks 26, 52, 78, 104, 130, 156,182, 208 (prior to study drug administration) until end of study (Up to 228 weeks)
measure: Trough Levels of Alpha1- Proteinase Inhibitor
timeFrame: 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)
Secondary outcomes:
Other outcomes:
Locations:
city: Aomori
country: Japan
facility: Hiroskai University Hospital
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Tokyo
country: Japan
facility: Juntendo University Hospital
Study officials:
References:
citation: 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.