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Alpha-1 Antitrypsin Deficiency (AATD)Phase 1/2NCT07227207

A Study of TSRA-196 in Adults With PiZZ Alpha-1 Antitrypsin Deficiency (AATD)

A Phase 1/2 study testing TSRA-196 in people with Alpha-1 Antitrypsin Deficiency (AATD), run by Tessera Therapeutics, Inc. at 9 sites in 4 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Alpha-1 Antitrypsin Deficiency (AATD)
What is being tested?
TSRA-196
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
9 sitesin 4 countries
Study dates
21 Apr 2026to Mar 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

9 sites in 4 countries. Contact the study team or a site near you to ask about taking part.

Tessera Clinical Trials Information contact

857-271-4800

clinicalinfo@tesseratx.com

9 sites in 4 countries

United States5 sites, 5 recruiting

  • Clinical Study Center

    Boston, Massachusetts, 02118

    Recruiting

  • Clinical Study Center

    Charleston, South Carolina, 29425

    Recruiting

  • Clinical Study Center

    Jacksonville, Florida, 32224

    Recruiting

  • Clinical Study Center

    Rochester, Minnesota, 55905

    Recruiting

  • Clinical Study Center

    Seattle, Washington, 98195

    Recruiting

Other trials in United States

United Kingdom2 sites, 2 recruiting

  • Clinical Study Center

    London

    Recruiting

  • Clinical Study Center

    Nottingham

    Recruiting

Other trials in United Kingdom

Australia1 site, 1 recruiting

  • Clinical Study Center

    Fitzroy, Victoria

    Recruiting

Other trials in Australia

Sweden1 site, 1 recruiting

  • Clinical Study Center

    Gothenburg

    Recruiting

Other trials in Sweden

About this study

Official title: 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

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)

Being tested
TSRA-196
Medical subject headings
alpha 1-Antitrypsin Deficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TSRA-196Drug

    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

Study groups in NCT07227207
Study groupRoleWhat they receive
TSRA-196 Drug ProductExperimentalNot described
Receives: Drug: TSRA-196

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1 (Dose Escalation): Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

    Measured: 1 Year

  2. 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 treatment

    Measured: 1 Year

  3. Part 2 (Dose Expansion): Change in functional AAT concentrations (determined using an elastase inhibition assay) from baseline to end of study

    Measured: 1 Year

  4. 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-196

    Measured: 1 Year

Secondary outcomes (14)

  1. Part 1 (Dose Escalation): Proportion of participants who have serum levels of total AAT greater than or equal to LLN after TSRA-196 treatment

    Measured: 1 Year

  2. Part 2 (Dose Expansion): Incidence of TEAEs and SAEs

    Measured: 1 Year

  3. Part 1 (Dose Escalation) and Part 2 (Dose Expansion): Proportion of participants who have serum levels of total AAT greater than or equal to 11 μM after TSRA-196 treatment

    Measured: 1 Year

  4. Part 1 (Dose Escalation) and Part 2 (Dose Expansion): Change in serum levels of total AAT from baseline over time

    Measured: 1 Year

  5. Part 1 (Dose Escalation) and Part 2 (Dose Expansion): Incidence of Adverse Event of Special Interest (AESI) from day of dosing through end of study

    Measured: 1 Year

  6. Part 1 (Dose Escalation) and Part 2 (Dose Expansion): Change over time in safety measures, including clinical laboratory parameters, vital signs, and ECG parameters

    Measured: 1 Year

  7. Part 1 (Dose Escalation) and Part 2 (Dose Expansion): Pharmacokinetic (PK) parameter: Area under the blood concentration time curves (AUC) of TSRA-196

    Measured: 1 Year

  8. Part 1 (Dose Escalation) and Part 2 (Dose Expansion): PK parameter: Maximum observed blood concentration (Cmax) of TSRA-196

    Measured: 1 Year

  9. Part 1 (Dose Escalation) and Part 2 (Dose Expansion): PK parameter: Time to Cmax (tmax) of TSRA-196

    Measured: 1 Year

  10. Part 1 (Dose Escalation) and Part 2 (Dose Expansion): PK parameter: Half-life (t1/2) of TSRA-196

    Measured: 1 Year

  11. Part 1 (Dose Escalation) and Part 2 (Dose Expansion): PK parameter: Clearance (CL) of TSRA-196

    Measured: 1 Year

  12. Part 1 (Dose Escalation) and Part 2 (Dose Expansion): PK parameter: The volume of distribution at terminal stage (Vz) of TSRA-196

    Measured: 1 Year

  13. Part 2 (Dose Expansion): Change in post-bronchodilator percent predicted forced expiratory volume (ppFEV1) from baseline through end of study

    Measured: 1 Year

  14. Part 2 (Dose Expansion): Incidence of COPD exacerbations from baseline over time

    Measured: 1 Year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Nov 2025
  2. Study start21 Apr 2026
  3. Primary completionMar 2029 (estimated)
  4. Study completionMar 2029 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
72 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07227207
Sponsor's protocol ID
TSRA196-AAT-201
Status last verified
Oct 2026
First submitted
3 Nov 2025
Last updated
2 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TSRA-196 in people with Alpha-1 Antitrypsin Deficiency (AATD), run by Tessera Therapeutics, Inc. at 9 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, United Kingdom, Australia, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Tessera Clinical Trials Information (857-271-4800, clinicalinfo@tesseratx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1 (Dose Escalation): Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) (time frame: 1 Year). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07227207.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.

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