AIR-001 treatment in adults with alpha-1 antitrypsin deficiency

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 Phase 1 trial will test single ascending and multiple doses of AIR-001 for safety and how the drug is processed in adults with PiZZ alpha-1 antitrypsin deficiency.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years to 74 Years
• Sex: All
• Sponsor: AIRNA Corporation (Industry-sponsored)
• Locations: 4 sites (Melbourne and 3 other locations)
• Trial ID: NCT07431112 on ClinicalTrials.gov

What this trial studies

This open-label Phase 1 study enrolls adults with Pi*ZZ alpha-1 antitrypsin deficiency to receive single ascending doses (SAD) followed by a multiple dose (MD) cohort of AIR-001. The protocol collects safety and tolerability data and measures pharmacokinetics (PK) and pharmacodynamics (PD) across dose levels. Eligible participants must have low serum AAT, confirmed Pi*ZZ genotype, adequate lung function (FEV1 ≥ 40% predicted), meet weight and BMI limits, and be non-smokers. Dosing and monitoring occur at clinical centers in Melbourne and Tbilisi with planned safety reviews between dose escalations.

Who should consider this trial

Good fit: Adults aged 18 to <75 years with confirmed Pi*ZZ genotype, total serum AAT <11 µM, FEV1 ≥ 40% predicted, body weight 45–110 kg, BMI 18–33 kg/m², and non-smokers are ideal candidates.

Not a fit: Patients with non-PiZZ genotypes, very advanced lung disease (FEV1 <40%), recent smokers, pregnant women, or those with disqualifying SERPINA1 variants are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, AIR-001 could offer a new therapeutic approach that improves AAT-related biology and potentially reduces lung or liver damage in PiZZ patients.

How similar studies have performed: Approved AAT augmentation therapy exists and other early-phase molecular approaches to AAT biology have shown some promising signals, but AIR-001 is a novel investigational agent with limited prior human data.

Eligibility criteria

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.

Where this trial is running

Melbourne and 3 other locations

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

Study contacts

• Study coordinator: AIRNA Corporation Clinical Trials Information

Conditions Alpha 1 Antitrypsin Deficiency; Lung Diseases; Liver Diseases; Respiratory Tract Diseases; Genetic Disease; Inborn Congenital, Hereditary, Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema