NCT07227207 · Tessera Therapeutics, Inc.
A Study of TSRA-196 in Adults With PiZZ Alpha-1 Antitrypsin Deficiency (AATD)
What this study is about
This is a Phase 1/2, where both patients and doctors know the treatment given, multi-center, gradually increasing doses (Part 1), dose expansion (Part 2), and single repeat dose (Part 3) study to evaluate the safety, tolerability, effectiveness, 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)
View original scientific description
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)
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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 criteria
- 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
Where
- Boston, Massachusetts
- Charleston, South Carolina
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 18, 2026 · Source of record for eligibility and locations