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

NCT07227207 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: TSRA196-AAT-201
• Study Type: interventional
• Target: 72
• Locations: 0 countries
• Sites: N/A

Brief 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)

Conditions

Alpha-1 Antitrypsin Deficiency (AATD)

Outcome Measures

Primary Outcomes (3)

• 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 treatment

  1 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-196

  1 Year

Secondary Outcomes (12)

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

  1 Year

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

  1 Year

• 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

  1 Year

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

  1 Year

• 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

  1 Year

Study Arms (1)

TSRA-196 Drug Product

EXPERIMENTAL

Drug: TSRA-196

Interventions

TSRA-196 DRUG

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

TSRA-196 Drug Product

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tessera Therapeutics, Inc.: lead

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2025
• First Posted: November 12, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: November 12, 2025

Record last verified: 2025-11