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) (SWIFT-SC)

An Open-Label, Multicenter, Randomized, Non-Inferiority Pharmacokinetic and Safety/Tolerability Study of Two Different Weekly Doses of Alpha1-Proteinase Inhibitor Subcutaneous (Human) 15% in Patients With Alpha1-Antitrypsin Deficiency Compared to Corresponding Standard 60 mg/kg/Week and 120 mg/kg/Week Doses of Intravenous Alpha1-Proteinase Inhibitor (5%)

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.

Study Overview

• Status: Recruiting
• Conditions: Alpha 1 Antitrypsin Deficiency
• Intervention / Treatment: Drug: Alpha-1 15%; Other: Liquid Alpha1-PI

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Elsa Mondou; Phone Number: +1 919 316 2079; Email: elsa.mondou@grifols.com
• Study Contact Backup: Name: Beatriz Garcia Castro; Phone Number: +(34) 670923669; Email: beatriz.garcia@grifols.com

Study Locations

• Denmark
  • Vejle, Denmark
    • Recruiting
    • Vijle Sygeheus
    • Principal Investigator: Ole Hilberg
    • Contact: Kamilla Krogh
• Ireland
  • Dublin, Ireland, D09YD60
    • Not yet recruiting
    • Beaumont Hospital
    • Contact: Ann Collins
    • Principal Investigator: McElvaney Noel Gerard
• Netherlands
  • Leiden, Netherlands
    • Not yet recruiting
    • Leiden University Medical Center
    • Contact: Tessa Hoekstra
    • Principal Investigator: Emily Van't Wout
• Poland
  • Warsaw, Poland
    • Not yet recruiting
    • Instytut Gruzlicy I Charób Pluc
    • Contact: Izabela Misiak
    • Principal Investigator: Joana Chorostowska
• Portugal
  • Guimarães, Portugal
    • Recruiting
    • Unidade Local de Saúde do Alto Ave
    • Contact: Beatriz Naivo
    • Principal Investigator: Caterina Guimaraes
  • Loures, Portugal
    • Recruiting
    • Unidade Local de Saúde Loures-Odivelas
    • Contact: Beatriz Cruz
    • Principal Investigator: Martin Teresa
• Spain
  • Madrid, Spain
    • Not yet recruiting
    • Hospital Clinico San Carlos
    • Contact: Juan Rodríguez Hermosa
    • Principal Investigator: Juan Rodríguez Hermosa
  • Vigo, Spain
    • Recruiting
    • Hospital Álvaro Cunqueiro
    • Contact: Ana Priegue Carrera
    • Principal Investigator: María Torres-Durán
• Sweden
  • Malmö, Sweden
    • Recruiting
    • Skåne University Hospital
    • Contact: Louise Qvist
    • Principal Investigator: Hanan Tanash
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Not yet recruiting
      • University of Alabama at Birmingham
      • Principal Investigator: J. Michael Wells, MD
      • Contact: Dianne Freeman
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Not yet recruiting
      • Pulmonary Associates
      • Contact: Liyi Fu
      • Principal Investigator: Da-Wei Liao, MD
    • Scottsdale, Arizona, United States, 85259
      • Not yet recruiting
      • Mayo Clinic
      • Contact: Ciara Terry
      • Principal Investigator: Garrett Ashley, MD
  • California
    • Los Angeles, California, United States, 90095
      • Not yet recruiting
      • UCLA
      • Principal Investigator: Igor Barjaktarevic, MD, PhD
      • Contact: Tiffany Bina
  • Florida
    • Gainesville, Florida, United States, 32610
      • Not yet recruiting
      • University of Florida
      • Principal Investigator: Jorge Lascano, MD
      • Contact: Brandi Lattinville
    • Miami, Florida, United States, 33136
      • Not yet recruiting
      • University of Miami
      • Principal Investigator: Michael Campos, MD
      • Contact: Tiffany Salcito
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Not yet recruiting
      • Mayo Clinic
      • Contact: Sam Fatis
      • Principal Investigator: Megan Dulohery-Scrodin, MD
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Not yet recruiting
      • Cleveland Clinic
      • Principal Investigator: Umur Hatipoglu, MD
      • Contact: Shauna Hendershot
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Not yet recruiting
      • Medical University of South Carolina
      • Principal Investigator: Charlie Strange, MD
      • Contact: Gwen Hayden
  • Texas
    • Dallas, Texas, United States, 75390
      • Not yet recruiting
      • UT Southwestern Medical Center
      • Contact: Rhoda Annoh Gordon
      • Principal Investigator: Carlos Cardenas, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm 1 (60 mg/kg/week of Liquid Alpha1-PI followed by 90 mg/kg/week of Alpha-1 15%); 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%; Alpha1-Proteinase Inhibitor Subcutaneous (Human), 15%; Other: Liquid Alpha1-PI; Liquid Alpha1-Proteinase Inhibitor (Human) for Intravenous infusion
Experimental: Treatment Arm 2 (120 mg/kg/week of Liquid Alpha1-PI followed by 180 mg/kg/week of Alpha-1 15%); 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%; Alpha1-Proteinase Inhibitor Subcutaneous (Human), 15%; Other: Liquid Alpha1-PI; Liquid Alpha1-Proteinase Inhibitor (Human) for Intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Grifols Therapeutics LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: April 21, 2026
• First Submitted That Met QC Criteria: April 21, 2026
• First Posted (Actual): April 29, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Respiratory Tract Diseases; Lung Diseases, Obstructive; Pathologic Processes; Subcutaneous; Lung Diseases; Clinical Trial; Genetic Diseases, Inborn; Protease Inhibitors; Intravenous; Phase 3; Pulmonary Disease, Chronic Obstructive; Emphysema; Pulmonary Emphysema; Molecular Mechanisms of Pharmacological Action; Serine Proteinase Inhibitors; Alpha 1-Antitrypsin; Subcutaneous Emphysema; Enzyme Inhibition; Alpha1-Proteinase Inhibitor (Human)
• Additional Relevant MeSH Terms: Chronic Disease; Disease Attributes; Digestive System Diseases; Liver Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Genetic Diseases, Inborn; Respiratory Tract Diseases; Pathologic Processes; Pulmonary Emphysema; Emphysema; alpha 1-Antitrypsin Deficiency; Subcutaneous Emphysema; 15-keto-17-phenyl-18,19,20-trinorprostaglandin F2 alpha-1-isopropyl ester
• Other Study ID Numbers: GC2501; 2025-522792-29-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No