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

Tessera Therapeutics, Inc.

Status and phase

Not yet enrolling

Phase 2

Phase 1

Conditions

Alpha-1 Antitrypsin Deficiency (AATD)

Treatments

Drug: TSRA-196

Study type

Interventional

Funder types

Industry

Identifiers

NCT07227207

TSRA196-AAT-201

Details and patient eligibility

About

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)

Enrollment

72 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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