A Non-inferiority Pharmacokinetic and Safety/Tolerability Study of Two Different Doses of Weekly SC Alpha1-PI 15% Compared With Corresponding Standard IV Alpha1-PI in Participants With Alpha1-Antitrypsin Deficiency (AATD)

NCT07555483 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: GC25012025-522792-29-00
• Study Type: interventional
• Target: 40
• Locations: 9 countries
• Sites: 22

Brief Summary

This study is designed to compare two different weekly doses of a medicine called Alpha1-Proteinase Inhibitor given by injection under the skin with the standard doses of the same medicine given through a vein. Adults with Alpha-1 Antitrypsin Deficiency will take part. Participants will be randomly assigned to one of the treatment groups, and both the study doctors and participants will know which treatment is being given. The main goals of the study are to understand how the body processes the medicine (pharmacokinetics) and to assess how safe and well tolerated the different weekly doses are.

Conditions

Alpha 1 Antitrypsin Deficiency

Keywords

Phase 3; Clinical Trial; Alpha1-Proteinase Inhibitor (Human); Alpha 1-Antitrypsin; Subcutaneous; Intravenous; Pulmonary Emphysema; Emphysema; Pathologic Processes; Pulmonary Disease, Chronic Obstructive; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Subcutaneous Emphysema; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibition; Molecular Mechanisms of Pharmacological Action

Outcome Measures

Primary Outcomes (1)

• 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

  Week 1 to Week 16

Secondary Outcomes (2)

• The average value of the steady-state trough alpha1-PI measurements obtained at Weeks 6, 7, 8, and 9 (Period 1)

  Weeks 6, 7, 8 and 9

• The average value of the steady-state trough alpha1-PI measurements obtained at Weeks 14, 15, 16, and 17 (Period 2)

  Weeks 14, 15, 16 and 17

Study Arms (2)

Treatment Arm 1 (60 mg/kg/week of Liquid Alpha1-PI followed by 90 mg/kg/week of Alpha-1 15%)

EXPERIMENTAL

8 weeks of IV treatment with 60 mg/kg/week Liquid Alpha1-PI followed by 8 weeks of SC treatment with 90 mg/kg/week Alpha-1 15%

Drug: Alpha-1 15%; Other: Liquid Alpha1-PI

Treatment Arm 2 (120 mg/kg/week of Liquid Alpha1-PI followed by 180 mg/kg/week of Alpha-1 15%)

EXPERIMENTAL

8 weeks of IV treatment with 120 mg/kg/week Liquid Alpha1-PI followed by 8 weeks of SC treatment with 180 mg/kg/week Alpha-1 15%

Drug: Alpha-1 15%; Other: Liquid Alpha1-PI

Interventions

Alpha-1 15% DRUG

Alpha1-Proteinase Inhibitor Subcutaneous (Human), 15%

Treatment Arm 1 (60 mg/kg/week of Liquid Alpha1-PI followed by 90 mg/kg/week of Alpha-1 15%); Treatment Arm 2 (120 mg/kg/week of Liquid Alpha1-PI followed by 180 mg/kg/week of Alpha-1 15%)

Liquid Alpha1-PI OTHER

Liquid Alpha1-Proteinase Inhibitor (Human) for Intravenous infusion

Treatment Arm 1 (60 mg/kg/week of Liquid Alpha1-PI followed by 90 mg/kg/week of Alpha-1 15%); Treatment Arm 2 (120 mg/kg/week of Liquid Alpha1-PI followed by 180 mg/kg/week of Alpha-1 15%)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.
• 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.
• All participants must have a documented total alpha1-PI serum level \<11 μM (80mg/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.
• At the Screening Visit, have post-bronchodilator Forced Expiratory Volume in 1 second (FEV₁) ≥25% and \<80% predicted of predicted FEV₁/Forced Vital Capacity (FVC) \<70% (Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] stage II-III, and some individuals are GOLD stage IV).
• 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.
• 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.

You may not qualify if:

• Have had a moderate or severe chronic obstructive pulmonary disease (COPD) exacerbation during the 4 weeks before the Week 1 (Baseline) Visit.
• Have history of lung or liver transplant or on transplantation waiting list.
• Have any lung surgery during the past 1 year (excluding lung biopsy).
• At screening, have elevated liver enzymes (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], and alkaline phosphatase \[ALP\]) ≥ 2.5 times the upper limit of normal (ULN).
• Have 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).
• 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. †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 \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\], declaration of abstinence for the duration of a study, and withdrawal are not acceptable methods of contraception.)
• 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.
• 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.
• Received 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.
• Have history of anaphylaxis or severe systemic response to any plasma-derived alpha1- PI preparation or other blood product(s).
• Use 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.
• Use systemic or aerosolized antibiotics for a COPD exacerbation within the 4 weeks prior to the Week 1 (Baseline) Visit.
• Have known selective or severe Immunoglobulin A (IgA) deficiency based on prior medical records.
• In 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.

Sponsors & Collaborators

• Grifols Therapeutics LLC: lead

Study Sites (22)

GC2501 Study Site 106

Birmingham, Alabama, 35233, United States

NOT YET RECRUITING

GC2501 Study Site 102

Phoenix, Arizona, 85032, United States

NOT YET RECRUITING

GC2501 Study Site 107

Scottsdale, Arizona, 85259, United States

NOT YET RECRUITING

GC2501 Study Site 100

Los Angelas, California, 90095, United States

NOT YET RECRUITING

GC2501 Study Site 103

Gainesville, Florida, 32610, United States

NOT YET RECRUITING

GC2501 Study Site 105

Miami, Florida, 33136, United States

NOT YET RECRUITING

GC2501 Study Site 108

Rochester, Minnesota, 55905, United States

NOT YET RECRUITING

GC2501 Study Site 104

Cleveland, Ohio, 44195, United States

NOT YET RECRUITING

GC2501 Study Site 101

Charleston, South Carolina, 29425, United States

NOT YET RECRUITING

GC2501 Study Site 109

Dallas, Texas, 75390, United States

NOT YET RECRUITING

GC2501 Study Site 150

Vejle, Denmark

RECRUITING

GC2501 Study Site 250

Freiburg im Breisgau, Germany

NOT YET RECRUITING

GC2501 Study Site 300

Dublin, D09YD60, Ireland

NOT YET RECRUITING

GC2501 Study Site 350

Leiden, Netherlands

RECRUITING

GC2501 Study Site 400

Warsaw, Poland

NOT YET RECRUITING

GC2501 Study Site 450

Guimarães, Portugal

RECRUITING

GC2501 Study Site 451

Loures, Portugal

RECRUITING

GC2501 Study Site 502

San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain

NOT YET RECRUITING

GC2501 Study Site 501

Madrid, Spain

NOT YET RECRUITING

GC2501 Study Site 503

Seville, Spain

NOT YET RECRUITING

GC2501 Study Site 500

Vigo, Spain

RECRUITING

GC2501 Study Site 550

Malmö, Sweden

RECRUITING

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency; Pulmonary Emphysema; Emphysema; Pathologic Processes; Pulmonary Disease, Chronic Obstructive; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Subcutaneous Emphysema

Interventions

15-keto-17-phenyl-18,19,20-trinorprostaglandin F2 alpha-1-isopropyl ester

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Chronic Disease; Disease Attributes

Central Study Contacts

Beatriz Garcia Castro

CONTACT

+(34) 670923669; beatriz.garcia@grifols.com

Lydia Martinez Garrido

CONTACT

+(34) 670929415; lydia.martinez@grifols.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2026
• First Posted: April 29, 2026
• Study Start: May 5, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: July 13, 2026

Record last verified: 2026-07

Locations

US (10); NL (1); PL (1); PT (2); DK (1); SE (1); ES (4); DE (1); IE (1)