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

NCT ID: NCT07227207

Last Updated: 2025-11-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-31
• Study Completion Date: 2029-03-31

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)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TSRA-196 Drug Product

Group Type: EXPERIMENTAL

TSRA-196

Intervention Type: 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

Interventions

TSRA-196

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tessera Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

TSRA196-AAT-201

Identifier Type: -

Identifier Source: org_study_id