HUMAN ALPHA1-PROTEINASE INHIBITOR for Alpha-1 antitrypsin deficiency

Inclusion criteria

• {"criterion_text":"- 1. At Screening Visit, is between 18 and 80 years of age, inclusive."}
• {"criterion_text":"- 2. Have a diagnosis of congenital AATD with an allelic combination of ZZ, SZ, Z(null), (null)(null), S(null), or “at-risk” alleles (patients with “at-risk” alleles listed in Appendix 2 must be individually evaluated for eligibility by the Medical Monitor). If the genotype has yet to be documented, a blood draw for genotyping (i.e., allelic discrimination) and phenotyping will be obtained at the Screening Visit."}
• {"criterion_text":"- 3. Participants may be naïve to Alpha1-PI augmentation therapy or may be currently receiving Alpha1-PI augmentation therapy or received Alpha1-PI augmentation therapy in the past. If the total alpha1-PI serum (alpha-1 antitrypsin [AAT]) level has yet to be documented as in a treatment-naïve patient, a blood draw for total alpha1-PI serum level will be obtained at the Screening Visit. For participants currently receiving Alpha1-PI augmentation, a pre-Alpha1-PI augmentation AAT level must be documented in the participant’s medical history/records."}
• {"criterion_text":"- 4. All participants must have a documented total alpha1-PI serum level <11 μM (80 mg/dL if measured by radial immunodiffusion or 50 mg/dL if measured by nephelometry) which is documented pre-Alpha1-PI augmentation for participants receiving AAT augmentation."}
• {"criterion_text":"- 5. At the Screening Visit, have a post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) ≥25% and <80% of predicted and FEV1/Forced Vital Capacity (FVC) <70% (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage II or III and some individuals who are GOLD stage IV)."}
• {"criterion_text":"- 6. If the participant has received alpha1-PI augmentation therapy of any kind, he/she must be willing to discontinue that treatment at the Week 1 (Baseline) Visit and remain off any kind of alpha1-PI treatment, other than the IPs of this study, while participating in the study."}
• {"criterion_text":"- 7. Willing and able to provide written informed consent indicating that they understand the purpose of, and procedures required for the study and are willing to participate in it."}

Exclusion criteria

• {"criterion_text":"- 1.\tHave had a moderate or severe chronic obstructive pulmonary disease (COPD) exacerbation during the 4 weeks before the Week 1 (Baseline) Visit."}
• {"criterion_text":"- 10.\tHave history of anaphylaxis or severe systemic response to any plasma-derived alpha1- PI preparation or other blood product(s)."}
• {"criterion_text":"- 11.\tUse systemic steroids above a stable dose equivalent to 5 mg/day prednisone (i.e., 10 mg every 2 days) within the 4 weeks prior to the Week 1 (Baseline) Visit (Note: inhaled steroids are not considered systemic steroids). It is recommended to maintain the same dose throughout the study."}
• {"criterion_text":"- 12.\tUse systemic or aerosolized antibiotics for a COPD exacerbation within the 4 weeks prior to the Week 1 (Baseline) Visit."}
• {"criterion_text":"- 13.\tHave known selective or severe Immunoglobulin A (IgA) deficiency based on prior medical records."}
• {"criterion_text":"- 14.\tIn the opinion of the Investigator, the participant may have compliance problems or any medical condition that may place them at safety risk with the protocol and the procedures of the protocol, or because of unstable health be unable to come to the study site for in-person clinic visits required by the protocol."}
• {"criterion_text":"- 2. Have history of lung or liver transplant or on transplantation waiting list."}
• {"criterion_text":"- 3. Have any lung surgery during the past 1 year (excluding lung biopsy)."}
• {"criterion_text":"- 4.\tAt screening, have elevated liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and alkaline phosphatase [ALP]) ≥ 2.5 times the upper limit of normal (ULN)."}
• {"criterion_text":"- 5.\tHave severe concomitant disease (e.g., congestive heart failure, clinically significant pulmonary fibrosis, malignant disease [except for skin cancers other than melanoma], history of acute hypersensitivity pneumonitis reaction, or current chronic hypersensitivity pneumonitis)."}
• {"criterion_text":"- 6.\tFemales 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. †Women of childbearing potential are defined as premenopausal and not surgically sterile, post tubal ligation, nor documented as infertile due to a concurrent medical condition. *True abstinence: When this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods], declaration of abstinence for the duration of a study, and withdrawal are not acceptable methods of contraception.)"}
• {"criterion_text":"- 7. Have known previous infection with or clinical signs and symptoms consistent with current Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV) infection."}
• {"criterion_text":"- 8. Have smoked during the past 6 months (this includes electronic/vapor cigarettes) or a positive urine cotinine test at the Screening Visit that is due to smoking."}
• {"criterion_text":"- 9.\tReceived IP in another study within 30 days prior to the Week 1 (Baseline) Visit or received any recombinant human AAT-Fc fusion protein (e.g., INBRX-101) or other extended half-life AAT products within 5 half-lives of the product relative to the Screening Visit date."}

Primary endpoints

• {"endpoint_text":"- The primary PK endpoint is the steady-state AUC of alpha1-PI over the weekly dosing interval (from 0 to 7 days) (AUC0-7 days) in the IV Treatment Period 1 and in the SC Treatment Period 2 for both dose levels.","definition_or_measurement_approach":"AUC0-7 days measured at steady-state; main objective describes measurement of alpha1-PI AUC using an antigenic content assay to compare SC 90 and 180 mg/kg/week vs IV 60 and 120 mg/kg/week over 8 weeks."}

Secondary endpoints

• {"endpoint_text":"- Steady-state mean trough alpha1-PI levels, following Liquid Alpha1-PI IV and Alpha-1 15% SC administration, determined as follows: • Liquid Alpha1-PI IV administration in Period 1: the average value of the steady-state trough alpha1-PI measurements obtained at Weeks 6, 7, 8, and 9. • Alpha-1 15% SC administration in Period 2: the average value of the steady-state trough alpha1-PI measurements obtained at Weeks 14, 15, 16, and 17.","definition_or_measurement_approach":"Mean trough alpha1-PI in steady-state defined as average of specified weekly trough measurements (Weeks 6–9 for IV; Weeks 14–17 for SC)."}
• {"endpoint_text":"- Exploratory Pharmacokinetic Endpoints: The following exploratory PK endpoints will be assessed in this study: • Cmax • tmax • CL for IV and CL/F for SC • t1/2 • Corrected AUC0-7 days, with correction based on the endogenous alpha1-PI concentration measured at Week 20 (4 weeks after the last IP infusion).","definition_or_measurement_approach":"Standard PK metrics: Cmax, tmax, clearance (CL for IV; CL/F for SC), terminal half-life (t1/2), and corrected AUC0-7 days with correction using endogenous alpha1-PI at Week 20 (4 weeks after last infusion)."}
• {"endpoint_text":"- Safety Endpoints: The following safety endpoints will be assessed in this study: • Adverse events (AEs), serious adverse events (SAEs), and AEs and SAEs leading to discontinuation • COPD exacerbations • Vital signs (heart rate [HR], blood pressure (BP), respiratory rate [RR], and temperature [T]) • Pulmonary function tests (PFTs)• Clinical laboratory parameters including: • Immunogenicity assessments","definition_or_measurement_approach":"Safety assessed by AEs/SAEs, COPD exacerbations, vital signs, pulmonary function tests, clinical labs and immunogenicity assessments as listed."}

Spain

Earliest CTIS Part Ii Submission Date

11-01-2026

Latest Decision Or Authorization Date

02-02-2026

Processing Time Days

22

Number Of Sites

2

Number Of Participants

2

Netherlands

Earliest CTIS Part Ii Submission Date

22-01-2026

Latest Decision Or Authorization Date

28-01-2026

Processing Time Days

6

Number Of Sites

1

Number Of Participants

10

Ireland

Earliest CTIS Part Ii Submission Date

22-12-2025

Latest Decision Or Authorization Date

30-01-2026

Processing Time Days

39

Number Of Sites

1

Number Of Participants

2

Poland

Earliest CTIS Part Ii Submission Date

08-01-2026

Latest Decision Or Authorization Date

30-01-2026

Processing Time Days

22

Number Of Sites

1

Number Of Participants

8

Sweden

Earliest CTIS Part Ii Submission Date

06-01-2026

Latest Decision Or Authorization Date

28-01-2026

Processing Time Days

22

Number Of Sites

1

Number Of Participants

9

Portugal

Earliest CTIS Part Ii Submission Date

11-01-2026

Latest Decision Or Authorization Date

28-01-2026

Processing Time Days

17

Number Of Sites

2

Number Of Participants

2

Denmark

Earliest CTIS Part Ii Submission Date

22-10-2025

Latest Decision Or Authorization Date

27-01-2026

Processing Time Days

97

Number Of Sites

1

Number Of Participants

5

Primary sponsor

Full Name

Grifols Therapeutics LLC

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Propharma Group LLC

Responsibilities

sponsorDuties codes: [1,2,5]

Name

Propharma Group The Netherlands B.V.

Responsibilities

sponsorDuties codes: [1]

Name

Bioagilytix Labs LLC

Responsibilities

sponsorDuties codes: [4]

Name

Labcorp Central Laboratory Services SARL

Responsibilities

sponsorDuties codes: [4]

Name

Swordbio

Responsibilities

sponsorDuties codes: [14,2]

Name

Veeva Systems Inc.

Responsibilities

sponsorDuties codes: [3,6,7]

Third parties

• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Propharma Group LLC","duties_or_roles":"sponsorDuties codes: [1,2,5]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Joshua Uhlorn","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"SME"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Swordbio","duties_or_roles":"sponsorDuties codes: [14,2]","organisation_type":"SME"}
• {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"sponsorDuties codes: [3,6,7]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Propharma Group The Netherlands B.V.","duties_or_roles":"sponsorDuties codes: [1]","organisation_type":"Pharmaceutical company"}