ALPHA-1-PROTEINASE INHIBITOR (HUMAN) for Pulmonary emphysema due to alpha-1 antitrypsin deficiency

Inclusion criteria

• {"criterion_text":"- At screening is between 18 and 70 years of age, inclusive."}
• {"criterion_text":"- Have a documented total alpha1-PI serum level < 11 μM. If the total alpha1-PI serum level has yet to be documented, a blood draw for total alpha1-PI serum level will be performed at the Screening (Week -3) Visit"}
• {"criterion_text":"- Have a diagnosis of congenital AATD with an allelic combination of ZZ, SZ, Z(null), (null)(null), S(null), or “at-risk” alleles. If the genotype has yet to be documented, genotyping and phenotyping will be performed at the Screening (Week -3) Visit."}
• {"criterion_text":"- At the Screening (Week -3) Visit, have a post-bronchodilator FEV1 ≥ 30% and < 80% of predicted and FEV1/FVC < 70% (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage II or III)."}
• {"criterion_text":"- Have a DLCO ≤ 60% of predicted (corrected for hemoglobin [HgB]) within the past 2 years OR evidence of pulmonary emphysema on CT scan within the past 2 years per the Investigator’s judgment."}
• {"criterion_text":"- Have a body mass index (BMI) < 40 kg/m2."}
• {"criterion_text":"- Willing and able to provide informed consent."}

Exclusion criteria

• {"criterion_text":"- Has received alpha1-PI augmentation therapy for more than 1 month within the 6 months prior to the Screening (Week -3) Visit."}
• {"criterion_text":"- Severe concomitant disease including, but not limited to, congestive heart failure and liver cirrhosis."}
• {"criterion_text":"- Malignant disease (including malignant melanoma; however, other forms of skin cancer are allowed) within five years of the Screening (Week -3) Visit."}
• {"criterion_text":"- Females who are 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 (IUD) or intrauterine system (IUS), condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or true abstinence*) throughout the study. * True abstinence: When this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods], declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception.)"}
• {"criterion_text":"- Has a metal object 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."}
• {"criterion_text":"- Currently infected with Hepatitis A virus (HAV) or Parvovirus B19 (B19V) or has laboratory results indicative of an acute or chronic infection with Hepatitis B virus (HBV), Hepatitis C virus (HCV), or Human Immunodeficiency Virus (HIV)."}
• {"criterion_text":"- Smoking, which includes electronic/vapor cigarettes, during the past 12 months or a positive urine cotinine test at screening that is due to smoking (Note: subjects who have a positive urine cotinine test and are also receiving nicotine replacement therapy (e.g., nicotine patches or chewing gum), or using snuff or snus (smokeless tobacco) may be eligible to participate in the study upon completion of an exhaled carbon monoxide [eCO] breath test; subjects with an eCO ≥ 10 ppm will be ineligible for study participation)."}
• {"criterion_text":"- History of chronic alcoholism or illicit drug abuse (addiction) in the 12 months prior to the Screening (Week -3) Visit."}
• {"criterion_text":"- Participation in another investigational product study within one month or five half-lives prior to the Screening (Week -3) Visit."}
• {"criterion_text":"- History of anaphylaxis or severe systemic response to any plasma-derived alpha1-PI preparation or other blood product(s)."}
• {"criterion_text":"- Use of systemic steroids above a stable dose equivalent to 5 mg/day prednisone (i.e., 10 mg every 2 days) within the 5 weeks prior to the Screening (Week -3) Visit (inhaled steroids are not considered systemic steroids) or during the Screening Phase. It is recommended to maintain the same dose throughout the study."}
• {"criterion_text":"- Has received alpha1-PI augmentation therapy within 1 month of the Screening (Week -3) Visit."}
• {"criterion_text":"- Use of systemic or aerosolized antibiotics for a COPD exacerbation within the 5 weeks prior to the Screening (Week -3) Visit or during the Screening Phase."}
• {"criterion_text":"- Known selective or severe Immunoglobulin A (IgA) deficiency."}
• {"criterion_text":"- Mentally challenged, adult subject who cannot give independent informed consent."}
• {"criterion_text":"- In the opinion of the Investigator the subject may have compliance problems with the protocol and the procedures of the protocol."}
• {"criterion_text":"- Any medical condition which the Investigator feels might confound the results of the study or pose an additional risk to the subject during study participation."}
• {"criterion_text":"- Has had a COPD exacerbation within the 5 weeks prior to the Screening (Week -3) Visit or during the Screening Phase. Investigator discretion should be used to determine if a subject is appropriate for study participation if the subject has had a COPD exacerbation which occurred more than 5 weeks prior to the Screening (Week -3) Visit."}
• {"criterion_text":"- Unable to physically (e.g., unable to fit inside the CT scanner) or mentally (e.g., claustrophobic) undergo a CT scan."}
• {"criterion_text":"- History of lung or liver transplant."}
• {"criterion_text":"- Any lung surgery during the past 2 years (excluding lung biopsy)."}
• {"criterion_text":"- On the waiting list for lung surgery, including lung transplant."}
• {"criterion_text":"- On the waiting list for liver transplant."}
• {"criterion_text":"- Elevated liver enzymes (aspartate transaminase [AST], alanine aminotransferase [ALT], and alkaline phosphatase) equal to or greater than 2.5 times the upper limit of normal (ULN)."}

Primary endpoints

• {"endpoint_text":"- The primary variable to assess efficacy in this study is whole lung PD15 using CT densitometry.","definition_or_measurement_approach":"Whole lung PD15 measured by CT densitometry (PD15 = 15th percentile lung density from CT)."}

Secondary endpoints

• {"endpoint_text":"- Severe COPD exacerbations as defined by ATS/ERS criteria (i.e., COPD exacerbations that require hospitalization)","definition_or_measurement_approach":"Incidence of severe COPD exacerbations as defined by ATS/ERS criteria (events requiring hospitalization)."}
• {"endpoint_text":"- PD15 of the basal lung region using CT densitometry.","definition_or_measurement_approach":"PD15 measured in the basal lung region via CT densitometry."}

Methods

• Doctor-to-patient letters (document: K2_Recruitment material_doctor to patient letter_for publ)
• Network advertising (document: K2_Recruitment Material_Network advertising)
• Alpha 1 Network advertising (document: K2_Recruitment material_Alpha 1 Network_Advertising)
• Recruitment via AATD register (document: L2_Other subject information material_Dr to Patient Letter AATD register)
• CTIS placeholder/standard recruitment arrangements documents (K1_Recruitment Arrangements_blank doc for CTIS placeholders for transitional trial)

Denmark

Earliest CTIS Part Ii Submission Date

16-08-2024

Latest Decision Or Authorization Date

22-08-2024

Processing Time Days

6

Number Of Sites

1

Number Of Participants

51

France

Earliest CTIS Part Ii Submission Date

16-08-2024

Latest Decision Or Authorization Date

23-08-2024

Processing Time Days

7

Number Of Sites

2

Number Of Participants

2

Poland

Earliest CTIS Part Ii Submission Date

16-08-2024

Latest Decision Or Authorization Date

01-10-2024

Processing Time Days

46

Number Of Sites

2

Number Of Participants

52

Sweden

Earliest CTIS Part Ii Submission Date

16-08-2024

Latest Decision Or Authorization Date

21-08-2024

Processing Time Days

5

Number Of Sites

2

Number Of Participants

62

Finland

Earliest CTIS Part Ii Submission Date

16-08-2024

Latest Decision Or Authorization Date

21-08-2024

Processing Time Days

5

Number Of Sites

1

Number Of Participants

3

Primary sponsor

Full Name

Grifols Therapeutics LLC

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

IQVIA Limited

Responsibilities

Sponsor duties codes: 1,12,2,6,7; CRO contact eu_clinical_trials_information@iqvia.com; phone 441184506016

Third parties

• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"codes: 1,12,2,6,7; contact eu_clinical_trials_information@iqvia.com; phone 441184506016","organisation_type":"Pharmaceutical company"}