Long Term Safety of Alpha1-Proteinase Inhibitor in Subjects With Alpha1 Antitrypsin Deficiency

Официальное название

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

Обзор

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).

Подробное описание

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.

Вмешательства

• Биопрепарат Alpha-1 MP
  Alpha-1 MP 60 mg/kg/week for up to 104 weeks

Первичные конечные точки

• Adverse events (AEs) [Срок оценки: Week 1 through Week 108]
• Serious AEs (SAEs) [Срок оценки: Week 1 through Week 108]
• Discontinuations from the study due to AEs [Срок оценки: Week 1 through Week 108]

Вторичные конечные точки (6)

• Change from baseline in whole lung PD15 (15th percentile point) [Срок оценки: Week 1 through Week 104]
• Change from baseline in carbon monoxide diffusing capacity (DLco) [Срок оценки: Week 52 and Week 104]
• Changes from baseline in forced expiratory volume in 1 second (FEV1) [Срок оценки: Week 52 and Week 104]
• Change from baseline in Saint George's Respiratory Questionnaire [Срок оценки: Week 52 and Week 104]
• Incidence and severity of Chronic Obstructive Pulmonary Disease (COPD)exacerbations [Срок оценки: Week 2 through Week 108]
• Change from baseline in the EQ-5D-5L Questionnaire [Срок оценки: Week 52 and Week 104]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 6 центров

• Grifols Investigative Site — Phoenix
• Grifols Investigative Site — Miami
• Grifols Investigative Site — Wilmington
• Grifols Investigative Site — Portland
• Grifols Investigative Site — Charleston
• Grifols Investigative Site — Tyler

Австралия · 5 центров

• Grifols Investigative Site — Darlinghurst
• Grifols Investigative Site — Adelaide
• Grifols Investigative Site — Chermside
• Grifols Investigative Site — Fitzroy
• Grifols Investigative Site — Nedlands

Новая Зеландия · 3 центра

• Grifols Investigative Site — Auckland
• Grifols Investigative Site — Christchurch
• Grifols Investigative Site — Hamilton

Швеция · 3 центра

• Grifols Investigative Site — Gothenburg
• Grifols Investigative Site — Malmö
• Grifols Investigative Site — Stockholm

Канада · 2 центра

• Grifols Investigative Site — Halifax
• Grifols Investigative Site — Toronto

Дания · 2 центра

• Grifols Investigative Site — Arhus C
• Grifols Investigative Site — Hellerup

Польша · 2 центра

• Grifols Investigative Site — Krakow
• Grifols Investigative Site — Warsaw

Эстония · 1 центр

• Grifols Investigative Site — Tallinn

Финляндия · 1 центр

• Grifols Investigative Site — Turku

Франция · 1 центр

• Grifols Investigative Site — Bron

Moldova · 1 центр

• Grifols Investigative Site — Chisinau

Россия · 1 центр

• Grifols Investigative Site — Barnaul

Идентификаторы

NCT: NCT02796937 · GTi1201-OLE

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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