Alpha 1 Antitrypsin DeficiencyPhase 1RepAIR1NCT07431112
A Study of AIR-001 in Adults With Alpha-1 Antitrypsin Deficiency (AATD)
A Phase 1 study testing AIR-001 SAD dose level 1, AIR-001 SAD dose level 2 and AIR-001 SAD dose level 3 in people with Alpha 1 Antitrypsin Deficiency, run by AIRNA Corporation at 13 sites in 9 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- Alpha 1 Antitrypsin Deficiency
- What is being tested?
- AIR-001 SAD dose level 1, AIR-001 SAD dose level 2 and AIR-001 SAD dose level 3
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 13 sitesin 9 countries
- Study dates
- 17 Mar 2026to Jan 2029
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female participants >18 years and <75 years of age at the time of signing informed consent
- Total serum AAT levels < 11µM (57 mg/dL)
- Pi*ZZ genotype confirmed by DNA sequencing within the SERPINA1 gene with no known co-occurring SERPINA1 null variants
- Spirometry: Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted
- Non-smoker, including vaping, for at least 6 months prior to screening
- Body mass index between 18-33.0 kg/m²
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- Body weight ≥ 45 kg and ≤110 kg
- Willing and able to give written informed consent prior to the initiation of any study procedure by the participant
- Negative beta human chorionic gonadotropin (β-hCG) at enrolment for women of childbearing potential (WOCBP) only.
- 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).
- Willing and able to comply with the study design schedule, all study procedures, and other requirements
Who cannot join
- Female participants who are nursing or lactating
- 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.
- Known or suspected allergy or intolerance to AIR-001 or its components
- 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.
- Positive screening test for COVID-19 and/or Influenza.
- 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.
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- 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.
- Any of the following screening laboratory abnormalities:
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma-glutamyl transferase (GGT) > 3 x upper limit of normal (ULN)
- 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)
- INR > ULN (for participants taking stable doses of anticoagulants, the exclusion criterion is INR > 3.0)
- Platelet count ≤ 150 k/μL
- Estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73m² by Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equation
- Urine Albumin-to-Creatinine Ratio > 300 mg/g
- Urine Protein-to-Creatinine Ratio > 500 mg/g
- Prolonged QT interval on electrocardiogram (ECG), defined as QTcF ≥ 450ms (men) or ≥ 470ms (women)
- ECG findings at screening that render measurements of QT interval imprecise.
- History of congestive heart failure, serious cardiac arrythmias requiring anti-arrhythmic medications or unexplained black-outs or fainting episodes with a suspected cardiac origin
- Positive screening test or known chronic infection with Hepatitis B, Hepatitis C, or HIV.
- Known history of coagulopathy or bleeding diathesis
- History or intolerance to subcutaneous (SC) injection including relevant dermatological conditions affecting standard injection sites
- 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.
- History of any lung-volume reduction procedure in the 6 months prior to screening.
- 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
- History of alcohol or drug abuse within the past three months
- 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
- Any previous gene replacement or DNA-editing therapy
- 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.
- 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.
Trial locations and contacts
13 sites in 9 countries. Contact the study team or a site near you to ask about taking part.
13 sites in 9 countries
United Kingdom3 sites, 3 recruiting
- Recruiting
Clinical Study Center
Cambridge
- Recruiting
Clinical Study Center
London
- Recruiting
Clinical Study Center
Southampton
Georgia2 sites
- Withdrawn
Clinical Study Center 1
Tbilisi
- Terminated
Clinical Study Center 2
Tbilisi
Germany2 sites, 2 recruiting
- Recruiting
Clinical Study Center
Hanover
- Recruiting
Clinical Study Center
Tübingen
Portugal1 site, 1 recruiting
- Recruiting
Clinical Study Center
Matosinhos Municipality
About this study
Official title: 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.
Read the detailed description
The study is designed to evaluate the safety, tolerability, PK, and PD of AIR-001.
- Conditions
- Alpha 1 Antitrypsin Deficiency
- Being tested
- AIR-001 SAD dose level 1, AIR-001 SAD dose level 2, AIR-001 SAD dose level 3, AIR-001 SAD dose level 4, AIR-001 MD dose level 1
- Keywords
- Lung Diseases, Liver Diseases, Respiratory Tract Diseases, Genetic Disease, Inborn Congenital, Hereditary, Neonatal Diseases and Abnormalities, Subcutaneous Emphysema, Emphysema, Pathologic Processes, Pathological Conditions, Signs and Symptoms, Alpha 1 Antitrypsin Deficiency
- Medical subject headings
- alpha 1-Antitrypsin Deficiency, Lung Diseases, Liver Diseases, Respiratory Tract Diseases, Genetic Diseases, Inborn, Infant, Newborn, Diseases, Congenital Abnormalities, Subcutaneous Emphysema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AIR-001 SAD dose level 1Drug
AIR-001 drug product, SC
AIR-001 SAD dose level 2Drug
AIR-001 drug product, SC
AIR-001 SAD dose level 3Drug
AIR-001 drug product, SC
AIR-001 SAD dose level 4Drug
AIR-001 drug product, SC
AIR-001 MD dose level 1Drug
AIR-001 drug product, SC
AIR-001 MD dose level 2Drug
AIR-001 drug product, SC
AIR-001 MD dose level 3Drug
AIR-001 drug product, SC
AIR-001 MD dose level 4Drug
AIR-001 drug product, SC
AIR-001 MD dose level 5Drug
AIR-001 drug product, SC
AIR-001 MD dose level 6Drug
AIR-001 drug product, SC
| Study group | Role | What they receive |
|---|---|---|
| AIR-001 SAD Cohort 1 | Experimental | AIR-001 is an RNA-editing oligonucleotide in sterile preservative-free solution administered by subcutaneous (SC) injection as a single dose. Receives: Drug: AIR-001 SAD dose level 1 |
| AIR-001 SAD Cohort 2 | Experimental | AIR-001 administered by SC injection as a single dose. Receives: Drug: AIR-001 SAD dose level 2 |
| AIR-001 SAD Cohort 3 | Experimental | AIR-001 administered by SC injection as a single dose. Receives: Drug: AIR-001 SAD dose level 3 |
| AIR-001 SAD Cohort 4 | Experimental | AIR-001 administered by SC injection, single dose. Receives: Drug: AIR-001 SAD dose level 4 |
| AIR-001 MD Cohort 1 | Experimental | AIR-001 is an RNA-editing oligonucleotide in sterile preservative-free solution administered by subcutaneous (SC) injection as multiple doses. Receives: Drug: AIR-001 MD dose level 1 |
| AIR-001 MD Cohort 2 | Experimental | AIR-001 administered by SC injection as multiple doses. Receives: Drug: AIR-001 MD dose level 2 |
| AIR-001 MD Cohort 3 | Experimental | AIR-001 administered by SC injection as multiple doses. Receives: Drug: AIR-001 MD dose level 3 |
| AIR-001 MD Cohort 4 | Experimental | AIR-001 administered by SC injection as multiple doses. Receives: Drug: AIR-001 MD dose level 4 |
| AIR-001 MD Cohort 5 | Experimental | AIR-001 administered by SC injection as multiple doses. Receives: Drug: AIR-001 MD dose level 5 |
| AIR-001 MD Cohort 6 | Experimental | AIR-001 administered by SC injection as multiple doses. Receives: Drug: AIR-001 MD dose level 6 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-emergent adverse events (TEAEs)
Measured: Up to Day 169
Incidence of laboratory abnormalities and shifts from baseline, including hematology, chemistry, coagulation, and urinalysis parameters
Measured: Baseline through up to Day 169
Incidence of abnormal vital signs
Measured: Baseline through up to Day 169
Incidence of abnormal electrocardiogram (ECG) findings
Measured: Baseline through up to Day 169
Secondary outcomes (3)
Area under the plasma concentration time curve for AIR-001 from time of dosing to the last measurable concentration (AUClast)
Measured: Up to Day 169
Maximum concentration of AIR-001 in plasma (Cmax)
Measured: Up to Day 169
Change from baseline in levels of total serum AAT protein, including serum M-AAT, Z-AAT, and functional AAT protein
Measured: Up to Day 169
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2026
- Study start17 Mar 2026
- Primary completionNov 2028 (estimated)
- Study completionJan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alpha 1 Antitrypsin DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AIRNA Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Information, Study director, AIRNA Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07431112
- Sponsor's protocol ID
- AIR-001-AATD-101
- Acronym
- RepAIR1
- Status last verified
- Sep 2026
- First submitted
- 19 Feb 2026
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No