Long Term Safety of Alpha1-Proteinase Inhibitor in Subjects With Alpha1 Antitrypsin Deficiency
- Conditions
- Pulmonary Emphysema in Alpha-1 Antitrypsin Deficiency
- Interventions
- Biological: Alpha-1 MP
- Registration Number
- NCT02796937
- Lead Sponsor
- Grifols Therapeutics LLC
- Brief Summary
This is a 2-year open-label, multicenter extension of the double-blind, placebo-controlled GTi1201 study. The purpose of this study is to obtain an additional 2 years of safety data for intravenously administered Alpha1-MP 60 mg/kg/week in subjects with alpha1-antitrypsin deficiency (AATD).
- Detailed Description
This is a 2-year open-label extension of the double-blind, placebo-controlled GTi1201 study. The purpose of this study is to obtain an additional 2 years of safety data for intravenously administered Alpha-1 MP 60 mg/kg/week in subjects with AATD.
The study consists of a Screening Visit (the same visit as the End-of-Study Visit in the GTi1201 study for subjects who complete the GTi1201 study or is the same visit as the Early Discontinuation Visit for subjects meeting the early withdrawal criterion for forced expiratory volume in 1 second \[FEV1\] decline), a treatment period of 104 weeks (beginning immediately after screening \[on the same day as the Screening Visit\] but no sooner than 1 week after the last infusion of investigational product in the GTi1201 study), and an End-of-Study Visit.
Subjects meeting the entrance criteria of the extension study will begin receiving weekly intravenous (IV) infusions of Alpha-1 MP 60 mg/kg on the day of screening and will continue to receive weekly infusions for a total of 104 infusions.
Safety assessments will include adverse events, concomitant medications, complete physical examination (excluding breast and genitourinary examination), hematology, chemistry, urine cotinine, and pregnancy test. Efficacy assessments will include whole lung computed tomography density, quality-of-life assessment, carbon monoxide diffusing capacity, and pulmonary function tests. The occurrence of chronic obstructive pulmonary exacerbations, will also be evaluated as a safety and as an efficacy measurement.
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 290
- Has completed participation in Study GTi1201 (ie, completed Week 156 and Week 160/End-of-Study Visit) OR has experienced a decline in FEV1 at the annualized rate of ≥134.4 mL/year at or after the Week 104 Visit in GTi1201.
- Is willing and able to provide informed consent
- Is unable to physically or mentally undergo a CT scan (eg, unable to fit inside the CT scanner, claustrophobic).
- Has severe concomitant disease including, but not limited to, congestive heart failure and liver cirrhosis.
- Has primary and/or secondary (metastatic disease) pulmonary malignancy or other current malignancy with <1 year predicted overall survival.
- Has a metal object (newly received since starting GTi1201) that might interfere with chest CT quality and quantification. Metal objects include, but are not limited to, cardiac pacemaker, defibrillator, metal prosthetic heart valve, metal projectile, metal weapon fragments, or metal shoulder prosthesis.
- Is a female who is 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 or intrauterine system; condom or occlusive cap with spermicidal foam/gel/film/cream/suppository; male sterilization; or abstinence) throughout the study.
- Has clinical signs and symptoms of viral infection requiring virus safety testing at the Week 160/End-of-Study Visit or Early Discontinuation Visit in Study GTi1201, and the virus safety test results are indicative of acute or chronic infection with hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), or parvovirus B19 (B19V). Note: If the virus safety test results are indicative of acute or chronic infection with HAV, HBV, HCV, HIV, or B19V, the subject will be considered a screen failure and must be withdrawn from the study.
- Has current evidence of smoking, which includes electronic/vapor cigarettes, or has a positive urine cotinine test at the Week 160/End-of- Study Visit in Study GTi1201 that is due to smoking.
- Has current evidence of chronic alcoholism or illicit drug abuse (addiction).
- Is currently participating in another investigational product (IP) study.
- Has a history of anaphylaxis or severe systemic response to any plasma- derived alpha1-PI preparation or other blood product(s).
- In the opinion of the investigator, is likely to have compliance problems with the protocol and the procedures of the protocol.
- Has any medical condition that the investigator feels might confound the results of the study or pose an additional risk to the subject during study participation.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Alpha-1 MP Alpha-1 MP Alpha-1 MP 60 mg/kg/week for up to 104 weeks
- Primary Outcome Measures
Name Time Method Discontinuations from the study due to AEs Week 1 through Week 108 Monitoring of discontinuations due to AEs
Adverse events (AEs) Week 1 through Week 108 Monitoring of AEs
Serious AEs (SAEs) Week 1 through Week 108 Monitoring of SAEs
- Secondary Outcome Measures
Name Time Method Change from baseline in the EQ-5D-5L Questionnaire Week 52 and Week 104 Heath-related quality of life assessment tool
Change from baseline in whole lung PD15 (15th percentile point) Week 1 through Week 104 Whole lung PD15 measured by computed tomography scans
Change from baseline in carbon monoxide diffusing capacity (DLco) Week 52 and Week 104 DLco performed according to American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines
Changes from baseline in forced expiratory volume in 1 second (FEV1) Week 52 and Week 104 FEV1 performed according to ATS/ERS guidelines
Change from baseline in Saint George's Respiratory Questionnaire Week 52 and Week 104 Health-related quality of life assessment tool
Incidence and severity of Chronic Obstructive Pulmonary Disease (COPD)exacerbations Week 2 through Week 108 Severe COPD exacerbations as defined by ATS/ERS guidelines
Trial Locations
- Locations (27)
Accellacare
🇺🇸Wilmington, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
The Prince Charles Hospital
🇦🇺Chermside, Australia
University of Texas Health Center at Tyler
🇺🇸Tyler, Texas, United States
St Vincent's Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
St Vincent's Hospital Melbourne
🇦🇺Fitzroy, Australia
Institute for Respiratory Health Inc
🇦🇺Nedlands, Australia
Inspiration Research Limited
🇨🇦Toronto, Canada
North Estonia Medical Centre Foundation
🇪🇪Tallinn, Estonia
Turun yliopistollinen keskussairaala
🇫🇮Turku, Finland
Christchurch Hospital NZ
🇳🇿Christchurch, New Zealand
CHU Lyon - Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel
🇫🇷Bron cedex, Rhone, France
NZ Respiratory and Sleep Institute
🇳🇿Auckland, New Zealand
Waikato Hospital
🇳🇿Hamilton, New Zealand
SPZOZ Szpital Uniwersytecki w Krakowie
🇵🇱Krakow, Poland
SBEI HPE Altai State Medical University of MoH and SD
🇷🇺Barnaul, Russian Federation
Sahlgrenska Sjukhuset
🇸🇪Göteborg, Sweden
Instytut Gruzlicy i Chorob Pluc w Warszawie
🇵🇱Warszawa, Poland
Skånes Universitetssjukhus, Malmö
🇸🇪Malmö, Sweden
Karolinska Trial Allicance, KTA Prim
🇸🇪Stockholm, Sweden
Arhus Universitetshospital
🇩🇰Arhus C, Denmark
Gentofte Hospital
🇩🇰Hellerup, Denmark
University Of Miami Hospital, Doctors Office West Building
🇺🇸Miami, Florida, United States
St. Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Queen Elizabeth II Health Sciences Centre
🇨🇦Halifax, Canada