A Study of TSRA-196 in Adults With PiZZ Alpha-1 Antitrypsin Deficiency (AATD)
Purpose
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)
Condition
- Alpha-1 Antitrypsin Deficiency (AATD)
Eligibility
- Eligible Ages
- Between 18 Years and 70 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental TSRA-196 Drug Product |
|
Recruiting Locations
Clinical Study Center
Boston, Massachusetts 02118
Boston, Massachusetts 02118
Clinical Study Center
Charleston, South Carolina 29425
Charleston, South Carolina 29425
More Details
- Status
- Recruiting
- Sponsor
- Tessera Therapeutics, Inc.