Long Term Safety of Alpha1-Proteinase Inhibitor in Subjects With Alpha1 Antitrypsin Deficiency (SPARTA-OLE)

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

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).

Study Overview

• Status: Enrolling by invitation
• Conditions: Pulmonary Emphysema in Alpha-1 Antitrypsin Deficiency
• Intervention / Treatment: Biological: Alpha-1 MP

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.

• Study Type: Interventional
• Enrollment (Estimated): 290
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Royal Adelaide Hospital
  • Chermside, Australia, 4032
    • The Prince Charles Hospital
  • Fitzroy, Australia, 3065
    • St Vincent's Hospital Melbourne
  • Nedlands, Australia, 6009
    • Institute for Respiratory Health Inc
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital Sydney
• Canada
  • Halifax, Canada, B3H 3A7
    • Queen Elizabeth Ii Health Sciences Centre
  • Toronto, Canada, M5T 3A9
    • Inspiration Research Limited
• Denmark
  • Arhus C, Denmark, 8000
    • Århus Universitetshospital
  • Hellerup, Denmark, 2900
    • Gentofte Hospital
• Estonia
  • Tallinn, Estonia, 13419
    • North Estonia Medical Centre Foundation
• Finland
  • Turku, Finland, 20520
    • Turun yliopistollinen keskussairaala
• France
  • Rhone
    • Bron cedex, Rhone, France, 69677
      • CHU Lyon - Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel
• New Zealand
  • Auckland, New Zealand, 2025
    • NZ Respiratory and Sleep Institute
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital NZ
  • Hamilton, New Zealand, 3200
    • Waikato Hospital
• Poland
  • Krakow, Poland, 31-066
    • SPZOZ Szpital Uniwersytecki w Krakowie
  • Warszawa, Poland, 01-138
    • Instytut Gruzlicy i Chorob Pluc w Warszawie
• Russian Federation
  • Barnaul, Russian Federation, 656038
    • SBEI HPE Altai State Medical University of MoH and SD
• Sweden
  • Göteborg, Sweden, 413 45
    • Sahlgrenska Sjukhuset
  • Malmö, Sweden, 20502
    • Skånes Universitetssjukhus, Malmo
  • Stockholm, Sweden, 11361
    • Karolinska Trial Allicance, KTA Prim
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University Of Miami Hospital, Doctors Office West Building
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Accellacare
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Tyler, Texas, United States, 75708
      • University of Texas Health Center at Tyler

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 72 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alpha-1 MP; Alpha-1 MP 60 mg/kg/week for up to 104 weeks	Biological: Alpha-1 MP; Alpha-1 MP 60 mg/kg/week for up to 104 weeks; Other Names: Prolastin-C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs)	Monitoring of AEs	Week 1 through Week 108
Serious AEs (SAEs)	Monitoring of SAEs	Week 1 through Week 108
Discontinuations from the study due to AEs	Monitoring of discontinuations due to AEs	Week 1 through Week 108

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in whole lung PD15 (15th percentile point)	Whole lung PD15 measured by computed tomography scans	Week 1 through Week 104
Change from baseline in carbon monoxide diffusing capacity (DLco)	DLco performed according to American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines	Week 52 and Week 104
Changes from baseline in forced expiratory volume in 1 second (FEV1)	FEV1 performed according to ATS/ERS guidelines	Week 52 and Week 104
Change from baseline in Saint George's Respiratory Questionnaire	Health-related quality of life assessment tool	Week 52 and Week 104
Incidence and severity of Chronic Obstructive Pulmonary Disease (COPD)exacerbations	Severe COPD exacerbations as defined by ATS/ERS guidelines	Week 2 through Week 108
Change from baseline in the EQ-5D-5L Questionnaire	Heath-related quality of life assessment tool	Week 52 and Week 104

Collaborators and Investigators

• Sponsor: Grifols Therapeutics LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: June 3, 2016
• First Submitted That Met QC Criteria: June 7, 2016
• First Posted (Estimated): June 13, 2016

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Alpha-1 Antitrypsin Deficiency; Pulmonary Emphysema; AATD; Alpha-1 PI Deficiency; Alpha-1 Proteinase Inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Liver Diseases; Genetic Diseases, Inborn; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Subcutaneous Emphysema; Chronic Disease; Pulmonary Emphysema; Emphysema; Alpha 1-Antitrypsin Deficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; Alpha 1-Antitrypsin
• Other Study ID Numbers: GTi1201-OLE