Trial Outcomes & Findings for Long-term Safety of Alpha1-Proteinase Inhibitor (Human) in Japanese Subjects With Alpha1 Antitrypsin Deficiency (GTI1401-OLE) (NCT NCT02870348)
NCT ID: NCT02870348
Last Updated: 2022-03-31
Results Overview
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.
COMPLETED
PHASE1/PHASE2
4 participants
From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
2022-03-31
Participant Flow
The study was conducted at 3 investigative sites in Japan from 29 July 2016 to 16 February 2021.
Participants with diagnosis of alpha1-antitrypsin deficiency (AATD) who completed the Study GTI1401 (NCT02870309) were eligible to enroll in this open-label extension study. The Screening / Extension (Ext) Week 1 Visit and initiation of treatment for the current study (GTI1401-OLE) occurred on the same day as the Week 9 Visit of GTI1401 only for those participants who gave the consent for participation in the Study GTI1401-OLE.
Participant milestones
| Measure |
Alpha-1 MP
Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks.
|
|---|---|
|
Overall Study
STARTED
|
4
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Alpha-1 MP
Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks.
|
|---|---|
|
Overall Study
Participants were discontinued and assessed for entry into post-marketing study (GTI1401-EXP)
|
4
|
Baseline Characteristics
Long-term Safety of Alpha1-Proteinase Inhibitor (Human) in Japanese Subjects With Alpha1 Antitrypsin Deficiency (GTI1401-OLE)
Baseline characteristics by cohort
| Measure |
Alpha-1 MP
n=4 Participants
Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks.
|
|---|---|
|
Age, Continuous
|
60.8 years
STANDARD_DEVIATION 5.56 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)Population: Safety Population included all participants who received any amount of Alpha-1 MP.
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.
Outcome measures
| Measure |
Alpha-1 MP
n=4 Participants
Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks.
|
|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
|
4 Participants
|
PRIMARY outcome
Timeframe: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)Population: Safety Population included all participants who received any amount of Alpha-1 MP.
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.
Outcome measures
| Measure |
Alpha-1 MP
n=4 Participants
Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks.
|
|---|---|
|
Number of Participants With Adverse Drug Reaction (ADRs)
|
2 Participants
|
PRIMARY outcome
Timeframe: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)Population: Safety Population included all participants who received any amount of Alpha-1 MP.
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.
Outcome measures
| Measure |
Alpha-1 MP
n=4 Participants
Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks.
|
|---|---|
|
Number of Participants With Serious Adverse Events (SAEs)
|
2 Participants
|
PRIMARY outcome
Timeframe: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)Population: Safety Population included all participants who received any amount of Alpha-1 MP.
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.
Outcome measures
| Measure |
Alpha-1 MP
n=4 Participants
Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks.
|
|---|---|
|
Number of Participants With Discontinuations Due to Adverse Events (AEs) or Serious Adverse Events (SAEs)
|
0 Participants
|
PRIMARY outcome
Timeframe: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)Population: Safety Population included all participants who received any amount of Alpha-1 MP.
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.
Outcome measures
| Measure |
Alpha-1 MP
n=4 Participants
Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks.
|
|---|---|
|
Number of Participants With Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
|
0 Participants
|
PRIMARY outcome
Timeframe: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)Population: Safety Population included all participants who received any amount of Alpha-1 MP.
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.
Outcome measures
| Measure |
Alpha-1 MP
n=4 Participants
Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks.
|
|---|---|
|
Number of Participants With Clinically Significant Findings in Vital Signs
|
0 Participants
|
PRIMARY outcome
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)Population: Safety Population included all participants who received any amount of Alpha-1 MP.
Clinical laboratory parameters included analysis of hematology, blood chemistry, and urinalysis. Clinically significant findings in clinical laboratory parameters were based on investigator's discretion.
Outcome measures
| Measure |
Alpha-1 MP
n=4 Participants
Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks.
|
|---|---|
|
Number of Participants With Clinically Significant Findings in Clinical Laboratory Parameters
|
0 Participants
|
PRIMARY outcome
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)Population: Safety Population included all participants who received any amount of Alpha-1 MP.
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.
Outcome measures
| Measure |
Alpha-1 MP
n=4 Participants
Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks.
|
|---|---|
|
Number of Participants With Clinically Significant Findings in Pulmonary Function Tests (PFTs)
|
0 Participants
|
PRIMARY outcome
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)Population: Safety Population included all participants who received any amount of Alpha-1 MP.
Alpha1-PI level was measured by nephelometry.
Outcome measures
| Measure |
Alpha-1 MP
n=4 Participants
Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks.
|
|---|---|
|
Trough Levels of Alpha1- Proteinase Inhibitor
|
55.734 milligram/deciliter (mg/dL)
Standard Deviation 4.9928
|
Adverse Events
Alpha-1 MP
Serious adverse events
| Measure |
Alpha-1 MP
n=4 participants at risk
Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks.
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Infections and infestations
Pneumonia
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Infections and infestations
Cellulitis
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Gastrointestinal disorders
Large intestine polyp
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
Other adverse events
| Measure |
Alpha-1 MP
n=4 participants at risk
Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks.
|
|---|---|
|
Cardiac disorders
Arrhythmia
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Cardiac disorders
Palpitations
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Eye disorders
Conjunctival haemorrhage
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Eye disorders
Eyelid pain
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Eye disorders
Vitreous floaters
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
50.0%
2/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Gastrointestinal disorders
Abdominal pain
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Gastrointestinal disorders
Diarrhoea
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Gastrointestinal disorders
Faeces soft
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Gastrointestinal disorders
Gastritis
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Gastrointestinal disorders
Haemorrhoids
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
50.0%
2/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Infections and infestations
Gastroenteritis
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Infections and infestations
Nasopharyngitis
|
50.0%
2/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Infections and infestations
Pharyngitis
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Injury, poisoning and procedural complications
Arthropod sting
|
50.0%
2/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Investigations
Blood creatinine increased
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Investigations
Influenza virus test positive
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Metabolism and nutrition disorders
Gout
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
50.0%
2/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
75.0%
3/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary mass
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
100.0%
4/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Vascular disorders
Hot flush
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
|
Infections and infestations
Pneumonia
|
25.0%
1/4 • From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Site may publish results from the Study, after providing Sponsor thirty days' notice prior to submitting a manuscript or other materials related to the Study to any outside party. At Sponsors' request, Site will remove any Confidential Information (other than Study results), and Site will upon Sponsors' request, delay publication or presentation for a period of up to one hundred twenty days to allow Sponsor to protect its interests in any Sponsor Inventions.
- Publication restrictions are in place
Restriction type: OTHER