A Study of TSRA-196 in Adults With PiZZ Alpha-1 Antitrypsin Deficiency (AATD)
A Phase 1/2, Open-Label, Multi-Center, Dose Escalation, Dose Expansion, and Single Repeat Dose Study of TSRA-196 in Adults With the PiZZ Genotype Who Have Lung and/or Liver Disease Associated With Severe Alpha-1 Antitrypsin Deficiency
Tessera Therapeutics, Inc.
72 participants
Apr 21, 2026
INTERVENTIONAL
Conditions
Summary
This is a Phase 1/2, open-label, multi-center, dose escalation (Part 1), dose expansion (Part 2), and single repeat dose (Part 3) study to evaluate the safety, tolerability, efficacy, and PK/PD parameters of TSRA-196 in adults with the PiZZ genotype who have lung and/or liver disease associated with severe alpha-1 antitrypsin deficiency (AATD)
Eligibility
Inclusion Criteria16
- Males or females who are 18 to 70 years of age, inclusive, at the time of signing the informed consent
- Body mass index of 18 to 37 kg/m2, inclusive
- Confirmed diagnosis of AATD and PiZZ genotype
- At least one previous measure of blood total AAT level <11 µmol/L
- Nonsmoker for at least 6 months before screening and must remain nonsmoking for the entire study duration
- Either AAT treatment-naïve or washed out of all investigational or approved treatments that modify AAT levels for 5 half-lives or at least 4 weeks, whichever is longer, before TSRA-196 administration
- Parts 1A and 2A (AATD lung disease with no or minimal liver fibrosis)
- Clinically significant lung disease, defined as 1) evidence of emphysema or bronchiectasis by computed tomography or 2) DLCO <70% of the predicted value or 3) ppFEV1 <80%
- ppFEV1 ≥35%
- METAVIR fibrosis score F0 or F1 confirmed by liver biopsy at screening, or a liver stiffness measure by FibroScan ≤7 kPa at screening
- FIB-4 index score ≤3.25 at screening
- ALT and/or AST <ULN at screening
- Parts 1B and 2B (AATD liver disease with significant or severe liver fibrosis, with or without AATD lung disease)
- METAVIR fibrosis score F2 or F3 confirmed by liver biopsy at screening. A liver biopsy conducted within 12 months before screening is acceptable as a substitute.
- Liver stiffness measure by FibroScan >7 and ≤15 kPa at screening
- ALT and/or AST <2 x ULN at screening
Exclusion Criteria13
- Presence of genetic variation in SERPINA1 gene that may disrupt the function of TSRA-196, determined by screening genotyping
- History of liver disease unrelated to AATD, or history of or clinical signs of cirrhosis
- Significant lung disease not attributable to manifestations of AATD, as determined by the investigator
- History of one or more hospitalizations due to severe exacerbation of underlying lung disease during the year before screening or received IV antibiotics for treatment of a pulmonary infection within 6 months before screening
- Unstable AATD-related COPD, as determined by the investigator, or severe bronchiectasis
- Lung volume reduction surgery within 1 year before screening or plan to receive lung volume reduction surgery during the study period
- Documented chronic need for positive airway pressure therapy beyond nocturnal use
- Seropositive for human immunodeficiency virus (HIV) (HIV-1 or HIV-2)
- Seropositive for hepatitis B (hepatitis B surface antigen \[HBsAg\] or hepatitis B core antibody \[HBcAb\] positive) with detectable HBV DNA
- Hepatitis C virus (HCV) RNA positive at screening (Parts 1A and 2A), or HCV RNA positive and/or HCV antibody positive at screening (Parts 1B and 2B)
- Has received an organ transplant or is on a waiting list for an organ transplant
- Prior treatment with gene therapy using viral vectors or intended to permanently change the patient's DNA
- Any investigational products within 30 days before dosing or plan to take an investigational product before the end of study
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Interventions
TSRA-196 is an in-vivo genome editing product formulated in lipid nanoparticles (LNPs) for the treatment of patients with alpha-1 antitrypsin deficiency (AATD), via intravenous (IV) infusion
Locations(3)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07227207