A Study of TSRA-196 for PiZZ Alpha-1 Antitrypsin Deficiency (AATD)
This study is testing a new treatment called TSRA-196 for adults with Alpha-1 Antitrypsin Deficiency (AATD) who have the PiZZ genotype. TSRA-196 is a gene-editing product given through an IV (intravenous) infusion. The study aims to see how safe TSRA-196 is and how well people tolerate it. It also looks at whether TSRA-196 can increase the levels of alpha-1 antitrypsin (AAT) in the blood to a normal range and improve its function. To join, you must be between 18 and 70 years old, have a confirmed PiZZ AATD diagnosis, and have low AAT levels. You also need to be a non-smoker. The current recruitment status is unclear.
- Study design
- This is a Phase 1/2, open-label study with 72 planned participants. It includes parts for increasing the dose, expanding the dose, and potentially repeating the dose.
- What's involved
- Participants will receive TSRA-196 through an IV infusion. Safety and AAT levels will be measured for up to 1 year.
- Compensation
- Not stated in the trial record.
- Follow-up
- Participants will be followed for safety and AAT levels for 1 year after treatment.
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NCT07227207
A Study of TSRA-196 in Adults With PiZZ Alpha-1 Antitrypsin Deficiency (AATD)
Recruiting
PHASE1Ages 18–70InterventionalTreatmentTessera Therapeutics, Inc.
~72 participants
Updated 2026-08-21 on ClinicalTrials.gov
What's tested:TSRA-196
At a glance
Recruiting sites
6 of 6 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Part 1 (Dose Escalation): Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Measured over 1 Year
+3 more outcomes measured
Conditions
Where it's being run
6 sites across 5 statesUnited Kingdom2
Massachusetts1
South Carolina1
Washington1
Victoria1
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
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
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
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
What this trial measures
- Part 1 (Dose Escalation): Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)1 Year
- Part 2 (Dose Expansion): Proportion of participants who have serum levels of total alpha-1 antitrypsin (AAT) greater than or equal to Lower Limit of Normal (LLN) after TSRA-196 treatment1 Year
- Part 2 (Dose Expansion): Change in functional AAT concentrations (determined using an elastase inhibition assay) from baseline to end of study1 Year
- Part 3 (Single Repeated Dose): Proportion of participants who have serum levels of total alpha-1 antitrypsin (AAT) greater than or equal to Lower Limit of Normal (LLN) after a second dose of TSRA-1961 Year