Clinical trial NCT02796937: Long Term Safety of Alpha1-Proteinase Inhibitor in Subjects With Alpha1 Antitrypsin Deficiency
Official title: An Open-Label, Multicenter Study to Evaluate the Long-term Safety of Weekly Intravenous Alpha1-Proteinase Inhibitor (Human), Modified Process 60 mg/kg in Subjects With Pulmonary Emphysema Due to Alpha1-Antitrypsin Deficiency
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Pulmonary Emphysema in Alpha-1 Antitrypsin Deficiency
Keywords: Pulmonary Emphysema
Alpha-1 Antitrypsin Deficiency
AATD
Alpha-1 PI Deficiency
Alpha-1 Proteinase Inhibitor
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2016-06-13
Enrollment: 290
Sex: ALL
Minimum age (years): 20
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Adverse events (AEs)
timeFrame: Week 1 through Week 108
measure: Serious AEs (SAEs)
timeFrame: Week 1 through Week 108
measure: Discontinuations from the study due to AEs
timeFrame: Week 1 through Week 108
Secondary outcomes:
measure: Change from baseline in whole lung PD15 (15th percentile point)
timeFrame: Week 1 through Week 104
measure: Change from baseline in carbon monoxide diffusing capacity (DLco)
timeFrame: Week 52 and Week 104
measure: Changes from baseline in forced expiratory volume in 1 second (FEV1)
timeFrame: Week 52 and Week 104
measure: Change from baseline in Saint George's Respiratory Questionnaire
timeFrame: Week 52 and Week 104
measure: Incidence and severity of Chronic Obstructive Pulmonary Disease (COPD)exacerbations
timeFrame: Week 2 through Week 108
measure: Change from baseline in the EQ-5D-5L Questionnaire
timeFrame: Week 52 and Week 104
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Miami
country: United States
facility: University Of Miami Hospital, Doctors Office West Building
state: Florida
city: Wilmington
country: United States
facility: Accellacare
state: North Carolina
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Tyler
country: United States
facility: University of Texas Health Center at Tyler
state: Texas
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Sydney
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Chermside
country: Australia
facility: The Prince Charles Hospital
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
city: Nedlands
country: Australia
facility: Institute for Respiratory Health Inc
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
city: Toronto
country: Canada
facility: Inspiration Research Limited
city: Arhus C
country: Denmark
facility: Arhus Universitetshospital
city: Hellerup
country: Denmark
facility: Gentofte Hospital
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre Foundation
city: Turku
country: Finland
facility: Turun yliopistollinen keskussairaala
city: Bron cedex
country: France
facility: CHU Lyon - Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel
state: Rhone
city: Auckland
country: New Zealand
facility: NZ Respiratory and Sleep Institute
city: Christchurch
country: New Zealand
facility: Christchurch Hospital NZ
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Krakow
country: Poland
facility: SPZOZ Szpital Uniwersytecki w Krakowie
city: Warszawa
country: Poland
facility: Instytut Gruzlicy i Chorob Pluc w Warszawie
city: Barnaul
country: Russian Federation
facility: SBEI HPE Altai State Medical University of MoH and SD
city: Göteborg
country: Sweden
facility: Sahlgrenska Sjukhuset
city: Malmö
country: Sweden
facility: Skånes Universitetssjukhus, Malmö
city: Stockholm
country: Sweden
facility: Karolinska Trial Allicance, KTA Prim
Study officials:
References: