A Study with an active treatment to Assess the Long-term Safety of Weekly Intravenous Product in Subjects with Pulmonary Emphysema due to Alpha1-Antitrypsin Deficiency

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Grifols Therapeutics LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

14 Jul 2016 → ongoing

Decision date (initial)

2024-08-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-513962-20-00

EudraCT number

2015-004110-23

ClinicalTrials.gov

NCT02796937

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objective 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.

Secondary objectives 1

1. The secondary objective of this study is to obtain an additional 2 years of data on disease progression in subjects with AATD intravenously administered Alpha-1 MP 60 mg/kg/week.

Conditions and MedDRA coding

Pulmonary Emphysema due to Alpha-1-Antitrypsin Deficiency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. a. Has completed participation in Study GTi1201 (ie, completed Week 156 and Week 160/End-of-Study Visit) Or b. Has experienced a decline in FEV1 at the annualized rate of ≥134.4 mL/year at or after the Week 104 Visit in GTi1201.
2. Is willing and able to provide informed consent.

Exclusion criteria 12

1. Is unable to physically or mentally undergo a CT scan (eg, unable to fit inside the CT scanner, claustrophobic).
2. Has severe concomitant disease including, but not limited to, congestive heart failure and liver cirrhosis.
3. Has primary and/or secondary (metastatic disease) pulmonary malignancy or other current malignancy with <1 year predicted overall survival
4. 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.
5. 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.
6. 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.
7. 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.
8. Has current evidence of chronic alcoholism or illicit drug abuse (addiction).
9. Is currently participating in another investigational product (IP) study.
10. Has a history of anaphylaxis or severe systemic response to any plasma-derived alpha1-PI preparation or other blood product(s).
11. In the opinion of the investigator, is likely to have compliance problems with the protocol and the procedures of the protocol.
12. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The efficacy variables that will be assessed are: •Whole lung 15th percentile point (PD15) using computed tomography (CT) densitometry •Carbon monoxide diffusing capacity (DLCO) •forced expiratory volume in 1 second (FEV1) •St. George’s Respiratory Questionnaire (SGRQ) score •Five level EQ-5D (EQ-5D-5L) score •Incidence and severity of chronic obstructive pulmonary disease (COPD) exacerbations as defined by American Thoracic Society (ATS)/European Respiratory Society (ERS) criteria

Secondary endpoints 1

1. The following safety variables will be assessed in this study: •AEs, serious AEs (SAEs), and discontinuations due to AEs and SAEs •Physical examination (complete and respiratory) •Clinical laboratory parameters: hematology, chemistry (includes high-sensitivity C-reactive protein [hs-CRP])

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Grifols Therapeutics LLC

Sponsor organisation

Grifols Therapeutics LLC

Address

79 Tw Alexander Drive

City

Durham

Postcode

27709-0152

Country

United States

Scientific contact point

Organisation

Grifols Therapeutics LLC

Contact name

SCIENTIFIC AND INNOVATION OFFICE DRUG DEVELOPMENT

Public contact point

Organisation

Grifols Therapeutics LLC

Contact name

SCIENTIFIC AND INNOVATION OFFICE DRUG DEVELOPMENT

Third parties 1

Locations

6 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 45 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications