A Study of AIR-001 in Adults With Alpha-1 Antitrypsin Deficiency (AATD) (RepAIR1)

Phase 1, Open-Label, Single Ascending Dose and Multiple Dose Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered AIR-001 in Adults With AATD Due to PiZZ Genotype

This is a Phase 1, open-label, single ascending dose (SAD) and multiple dose (MD) study of AIR-001 in participants with alpha-1 antitrypsin deficiency (AATD) due to PiZZ genotype.

Study Overview

• Status: Recruiting
• Conditions: Alpha 1 Antitrypsin Deficiency
• Intervention / Treatment: Drug: AIR-001 SAD dose level 1; Drug: AIR-001 SAD dose level 2; Drug: AIR-001 SAD dose level 3; Drug: AIR-001 SAD dose level 4; Drug: AIR-001 MD dose level 1; Drug: AIR-001 MD dose level 2; Drug: AIR-001 MD dose level 3; Drug: AIR-001 MD dose level 4; Drug: AIR-001 MD dose level 5; Drug: AIR-001 MD dose level 6

Detailed Description

The study is designed to evaluate the safety, tolerability, PK, and PD of AIR-001.

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: AIRNA Corporation Clinical Trials Information; Phone Number: 617-609-8790; Email: patients@airna.com

Study Locations

• Australia
  • Melbourne, Australia
    • Recruiting
    • Clinical Study Center
• Georgia
  • Tbilisi, Georgia
    • Recruiting
    • Clinical Study Center 1
  • Tbilisi, Georgia
    • Recruiting
    • Clinical Study Center 2
• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Clinical Study Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male or female participants >18 years and <75 years of age at the time of signing informed consent
2. Total serum AAT levels < 11µM (57 mg/dL)
3. Pi*ZZ genotype confirmed by DNA sequencing within the SERPINA1 gene with no known co-occurring SERPINA1 null variants
4. Spirometry: Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted
5. Non-smoker, including vaping, for at least 6 months prior to screening
6. Body mass index between 18-33.0 kg/m²
7. Body weight ≥ 45 kg and ≤110 kg
8. Willing and able to give written informed consent prior to the initiation of any study procedure by the participant
9. Negative beta human chorionic gonadotropin (β-hCG) at enrolment for women of childbearing potential (WOCBP) only.
10. Participants who are either a WOCBP or male participant who is heterosexually active with a WOCBP must consent to use a highly effective method of contraception from screening visit until at least 4 weeks after the last dose of investigational medicinal product (IMP).
11. Willing and able to comply with the study design schedule, all study procedures, and other requirements

Exclusion Criteria:

1. Female participants who are nursing or lactating
2. Participant has received AAT augmentation therapy within 30 days prior to Screening Visit or plans to receive AAT augmentation therapy at any time during study participation.
3. Known or suspected allergy or intolerance to AIR-001 or its components
4. Acute respiratory tract infection or clinically-diagnosed chronic obstructive pulmonary disease (COPD) exacerbation that required antibiotic treatment and/or systemic corticosteroids within the 8 weeks prior to dosing.
5. Positive screening test for COVID-19 and/or Influenza.
6. Lung disease that requires use of continuous oral corticosteroids, continuous supplemental oxygen, day-time ventilatory support, or any participant who is on a lung transplant waiting list.
7. Liver Fibrosis score > 10 kPa defined by screening liver elastography, historical liver biopsy showing ≥ F3 fibrosis (METAVIR or comparable scoring system), or established diagnosis of hepatic cirrhosis.

8. Any of the following screening laboratory abnormalities:

   1. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma-glutamyl transferase (GGT) > 3 x upper limit of normal (ULN)
   2. Total bilirubin > ULN (note: for participants with documented Gilbert's syndrome and direct bilirubin ≤ ULN , exclusion criterion is total bilirubin is > 2.5 mg/dL)
   3. INR > ULN (for participants taking stable doses of anticoagulants, the exclusion criterion is INR > 3.0)
   4. Platelet count ≤ 150 k/μL
   5. Estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73m² by Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equation
   6. Urine Albumin-to-Creatinine Ratio > 300 mg/g
   7. Urine Protein-to-Creatinine Ratio > 500 mg/g
9. Prolonged QT interval on electrocardiogram (ECG), defined as QTcF ≥ 450ms (men) or ≥ 470ms (women)
10. ECG findings at screening that render measurements of QT interval imprecise.
11. History of congestive heart failure, serious cardiac arrythmias requiring anti-arrhythmic medications or unexplained black-outs or fainting episodes with a suspected cardiac origin
12. Positive screening test or known chronic infection with Hepatitis B, Hepatitis C, or HIV.
13. Known history of coagulopathy or bleeding diathesis
14. History or intolerance to subcutaneous (SC) injection including relevant dermatological conditions affecting standard injection sites
15. History or presence of any medical condition, behavioral or psychiatric disorder, or planned surgical procedure or surgical history that may interfere with participation in the study or interpretation of study results, and/or put the participant at significant risk (in the opinion of the investigator) if he/she participates in the study.
16. History of any lung-volume reduction procedure in the 6 months prior to screening.
17. Laboratory value(s) outside the laboratory reference range that is (are) considered to be clinically significant and may affect the safety, efficacy, PK, or PD assessments or interpretation by the Investigator, at screening
18. History of alcohol or drug abuse within the past three months
19. Current or previous participation in any other clinical study where the participant has received a dose of an IMP within 3 months or 5 half-lives of the IMP, whichever is longest, prior to Screening Visit
20. Any previous gene replacement or DNA-editing therapy
21. Any previous use of an RNA-based therapeutic (except for AIR-001 or RNA-based vaccines) within the 6 months prior to the Screening Visit or at any time if stopped due to drug-related adverse event.
22. Use of any new prescription, vaccine, herbal remedy, over-the-counter medication, or supplement, or changes in chronic therapies within the 28 days prior to dosing unless approved by study Medical Monitor.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AIR-001 SAD Cohort 1; AIR-001 is an RNA-editing oligonucleotide in sterile preservative-free solution administered by subcutaneous (SC) injection as a single dose.	Drug: AIR-001 SAD dose level 1; AIR-001 drug product, SC
Experimental: AIR-001 SAD Cohort 2; AIR-001 administered by SC injection as a single dose.	Drug: AIR-001 SAD dose level 2; AIR-001 drug product, SC
Experimental: AIR-001 SAD Cohort 3; AIR-001 administered by SC injection as a single dose.	Drug: AIR-001 SAD dose level 3; AIR-001 drug product, SC
Experimental: AIR-001 SAD Cohort 4; AIR-001 administered by SC injection, single dose.	Drug: AIR-001 SAD dose level 4; AIR-001 drug product, SC
Experimental: AIR-001 MD Cohort 1; AIR-001 is an RNA-editing oligonucleotide in sterile preservative-free solution administered by subcutaneous (SC) injection as multiple doses.	Drug: AIR-001 MD dose level 1; AIR-001 drug product, SC
Experimental: AIR-001 MD Cohort 2; AIR-001 administered by SC injection as multiple doses.	Drug: AIR-001 MD dose level 2; AIR-001 drug product, SC
Experimental: AIR-001 MD Cohort 3; AIR-001 administered by SC injection as multiple doses.	Drug: AIR-001 MD dose level 3; AIR-001 drug product, SC
Experimental: AIR-001 MD Cohort 4; AIR-001 administered by SC injection as multiple doses.	Drug: AIR-001 MD dose level 4; AIR-001 drug product, SC
Experimental: AIR-001 MD Cohort 5; AIR-001 administered by SC injection as multiple doses.	Drug: AIR-001 MD dose level 5; AIR-001 drug product, SC
Experimental: AIR-001 MD Cohort 6; AIR-001 administered by SC injection as multiple doses.	Drug: AIR-001 MD dose level 6; AIR-001 drug product, SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with treatment-emergent adverse events (TEAEs)	Up to Day 169
Incidence of laboratory abnormalities and shifts from baseline, including hematology, chemistry, coagulation, and urinalysis parameters	Baseline through up to Day 169
Incidence of abnormal vital signs	Baseline through up to Day 169
Incidence of abnormal electrocardiogram (ECG) findings	Baseline through up to Day 169

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration time curve for AIR-001 from time of dosing to the last measurable concentration (AUClast)	Up to Day 169
Maximum concentration of AIR-001 in plasma (Cmax)	Up to Day 169
Change from baseline in levels of total serum AAT protein, including serum M-AAT, Z-AAT, and functional AAT protein	Up to Day 169

Collaborators and Investigators

• Sponsor: AIRNA Corporation
• Investigators: Study Director: Clinical Information, AIRNA Corporation

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: February 19, 2026
• First Submitted That Met QC Criteria: February 19, 2026
• First Posted (Actual): February 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Respiratory Tract Diseases; Pathologic Processes; Lung Diseases; Liver Diseases; Emphysema; Genetic Disease; Subcutaneous Emphysema; Pathological Conditions, Signs and Symptoms; Inborn Congenital, Hereditary, Neonatal Diseases and Abnormalities; Alpha 1 Antitrypsin Deficiency
• Additional Relevant MeSH Terms: Digestive System Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Congenital Abnormalities; Lung Diseases; Genetic Diseases, Inborn; Liver Diseases; Respiratory Tract Diseases; Pathologic Processes; Emphysema; Infant, Newborn, Diseases; alpha 1-Antitrypsin Deficiency; Pathological Conditions, Signs and Symptoms; Subcutaneous Emphysema
• Other Study ID Numbers: AIR-001-AATD-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No