[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT07227207":3,"trial-entities:NCT07227207":164,"trial-summary:NCT07227207":169},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":20,"study_type":21,"primary_purpose":22,"phases":23,"enrollment_info":26,"interventions":29,"primary_outcomes":36,"secondary_outcomes":46,"sex":75,"minimum_age":76,"maximum_age":77,"healthy_volunteers":78,"eligibility_criteria":79,"std_ages":110,"locations":113,"central_contacts":155,"overall_officials":161,"references":162,"see_also_links":163},"NCT07227207","TSRA196-AAT-201","A Study of TSRA-196 in Adults With PiZZ Alpha-1 Antitrypsin Deficiency (AATD)","A Phase 1\u002F2, 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\u002For Liver Disease Associated With Severe Alpha-1 Antitrypsin Deficiency","RECRUITING","2029-03","2026-08","2026-08-21","2026-04-21","Tessera Therapeutics, Inc.","INDUSTRY",true,"This is a Phase 1\u002F2, 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\u002FPD parameters of TSRA-196 in adults with the PiZZ genotype who have lung and\u002For liver disease associated with severe alpha-1 antitrypsin deficiency (AATD)",null,[19],"Alpha-1 Antitrypsin Deficiency (AATD)",[],"INTERVENTIONAL","TREATMENT",[24,25],"PHASE1","PHASE2",{"count":27,"type":28},72,"ESTIMATED",[30],{"type":31,"name":32,"description":33,"armGroupLabels":34},"DRUG","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",[35],"TSRA-196 Drug Product",[37,40,42,44],{"measure":38,"timeFrame":39},"Part 1 (Dose Escalation): Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)","1 Year",{"measure":41,"timeFrame":39},"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",{"measure":43,"timeFrame":39},"Part 2 (Dose Expansion): Change in functional AAT concentrations (determined using an elastase inhibition assay) from baseline to end of study",{"measure":45,"timeFrame":39},"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",[47,49,51,53,55,57,59,61,63,65,67,69,71,73],{"measure":48,"timeFrame":39},"Part 1 (Dose Escalation): Proportion of participants who have serum levels of total AAT greater than or equal to LLN after TSRA-196 treatment",{"measure":50,"timeFrame":39},"Part 2 (Dose Expansion): Incidence of TEAEs and SAEs",{"measure":52,"timeFrame":39},"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",{"measure":54,"timeFrame":39},"Part 1 (Dose Escalation) and Part 2 (Dose Expansion): Change in serum levels of total AAT from baseline over time",{"measure":56,"timeFrame":39},"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",{"measure":58,"timeFrame":39},"Part 1 (Dose Escalation) and Part 2 (Dose Expansion): Change over time in safety measures, including clinical laboratory parameters, vital signs, and ECG parameters",{"measure":60,"timeFrame":39},"Part 1 (Dose Escalation) and Part 2 (Dose Expansion): Pharmacokinetic (PK) parameter: Area under the blood concentration time curves (AUC) of TSRA-196",{"measure":62,"timeFrame":39},"Part 1 (Dose Escalation) and Part 2 (Dose Expansion): PK parameter: Maximum observed blood concentration (Cmax) of TSRA-196",{"measure":64,"timeFrame":39},"Part 1 (Dose Escalation) and Part 2 (Dose Expansion): PK parameter: Time to Cmax (tmax) of TSRA-196",{"measure":66,"timeFrame":39},"Part 1 (Dose Escalation) and Part 2 (Dose Expansion): PK parameter: Half-life (t1\u002F2) of TSRA-196",{"measure":68,"timeFrame":39},"Part 1 (Dose Escalation) and Part 2 (Dose Expansion): PK parameter: Clearance (CL) of TSRA-196",{"measure":70,"timeFrame":39},"Part 1 (Dose Escalation) and Part 2 (Dose Expansion): PK parameter: The volume of distribution at terminal stage (Vz) of TSRA-196",{"measure":72,"timeFrame":39},"Part 2 (Dose Expansion): Change in post-bronchodilator percent predicted forced expiratory volume (ppFEV1) from baseline through end of study",{"measure":74,"timeFrame":39},"Part 2 (Dose Expansion): Incidence of COPD exacerbations from baseline over time","ALL","18 Years","70 Years",false,{"inclusion":80,"exclusion":95,"raw_text":109},[81,82,83,84,85,86,87,88,89,90,91,92,93,94],"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\u002Fm2, inclusive","Confirmed diagnosis of AATD and PiZZ genotype","At least one previous measure of blood total AAT level \\\u003C11 µmol\u002FL","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","Clinically significant lung disease, defined as 1) evidence of emphysema or bronchiectasis by computed tomography or 2) DLCO \\\u003C70% of the predicted value or 3) ppFEV1 \\\u003C80%","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\u002For AST \\\u003CULN at screening","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\u002For AST \\\u003C2 x ULN at screening",[96,97,98,99,100,101,102,103,104,105,106,107,108],"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\u002For 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","Inclusion Criteria:\n\n* Males or females who are 18 to 70 years of age, inclusive, at the time of signing the informed consent\n* Body mass index of 18 to 37 kg\u002Fm2, inclusive\n* Confirmed diagnosis of AATD and PiZZ genotype\n* At least one previous measure of blood total AAT level \\\u003C11 µmol\u002FL\n* Nonsmoker for at least 6 months before screening and must remain nonsmoking for the entire study duration\n* 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\n\nParts 1A and 2A (AATD lung disease with no or minimal liver fibrosis)\n\n* Clinically significant lung disease, defined as 1) evidence of emphysema or bronchiectasis by computed tomography or 2) DLCO \\\u003C70% of the predicted value or 3) ppFEV1 \\\u003C80%\n* ppFEV1 ≥35%\n* METAVIR fibrosis score F0 or F1 confirmed by liver biopsy at screening, or a liver stiffness measure by FibroScan ≤7 kPa at screening\n* FIB-4 index score ≤3.25 at screening\n* ALT and\u002For AST \\\u003CULN at screening\n\nParts 1B and 2B (AATD liver disease with significant or severe liver fibrosis, with or without AATD lung disease)\n\n* 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.\n* Liver stiffness measure by FibroScan \\>7 and ≤15 kPa at screening\n* ALT and\u002For AST \\\u003C2 x ULN at screening\n\nExclusion Criteria:\n\n* Presence of genetic variation in SERPINA1 gene that may disrupt the function of TSRA-196, determined by screening genotyping\n* History of liver disease unrelated to AATD, or history of or clinical signs of cirrhosis\n* Significant lung disease not attributable to manifestations of AATD, as determined by the investigator\n* 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\n* Unstable AATD-related COPD, as determined by the investigator, or severe bronchiectasis\n* Lung volume reduction surgery within 1 year before screening or plan to receive lung volume reduction surgery during the study period\n* Documented chronic need for positive airway pressure therapy beyond nocturnal use\n* Seropositive for human immunodeficiency virus (HIV) (HIV-1 or HIV-2)\n* Seropositive for hepatitis B (hepatitis B surface antigen \\[HBsAg\\] or hepatitis B core antibody \\[HBcAb\\] positive) with detectable HBV DNA\n* Hepatitis C virus (HCV) RNA positive at screening (Parts 1A and 2A), or HCV RNA positive and\u002For HCV antibody positive at screening (Parts 1B and 2B)\n* Has received an organ transplant or is on a waiting list for an organ transplant\n* Prior treatment with gene therapy using viral vectors or intended to permanently change the patient's DNA\n* Any investigational products within 30 days before dosing or plan to take an investigational product before the end of study",[111,112],"ADULT","OLDER_ADULT",[114,123,130,137,144,150],{"facility":115,"status":8,"city":116,"state":117,"zip":118,"country":119,"geoPoint":120},"Clinical Study Center","Boston","Massachusetts","02118","United States",{"lat":121,"lon":122},42.35843,-71.05977,{"facility":115,"status":8,"city":124,"state":125,"zip":126,"country":119,"geoPoint":127},"Charleston","South Carolina","29425",{"lat":128,"lon":129},32.77632,-79.93275,{"facility":115,"status":8,"city":131,"state":132,"zip":133,"country":119,"geoPoint":134},"Seattle","Washington","98195",{"lat":135,"lon":136},47.60621,-122.33207,{"facility":115,"status":8,"city":138,"state":139,"country":140,"geoPoint":141},"Fitzroy","Victoria","Australia",{"lat":142,"lon":143},-37.79839,144.97833,{"facility":115,"status":8,"city":145,"country":146,"geoPoint":147},"London","United Kingdom",{"lat":148,"lon":149},51.50853,-0.12574,{"facility":115,"status":8,"city":151,"country":146,"geoPoint":152},"Nottingham",{"lat":153,"lon":154},52.9536,-1.15047,[156],{"name":157,"role":158,"phone":159,"email":160},"Tessera Clinical Trials Information","CONTACT","857-271-4800","clinicalinfo@tesseratx.com",[],[],[],{"nct_id":4,"conditions":165,"biomarkers":167},[166],"Alpha-1 Antitrypsin Deficiency",[168],"SERPINA1 Gene",{"nct_id":4,"found":15,"summary":170,"prompt_version":180},{"design":171,"status":172,"heading":173,"summary":174,"follow_up":175,"word_count":176,"commitments":177,"compensation":178,"drugs_mentioned":179},"This is a Phase 1\u002F2, open-label study with 72 planned participants. It includes parts for increasing the dose, expanding the dose, and potentially repeating the dose.","completed","A Study of TSRA-196 for PiZZ Alpha-1 Antitrypsin Deficiency (AATD)","This study is testing a new treatment called TSRA-196 for adults with Alpha-1 Antitrypsin Deficiency (AATD) who have the PiZZ genotype. TSRA-196 is a gene-editing product given through an IV (intravenous) infusion. The study aims to see how safe TSRA-196 is and how well people tolerate it. It also looks at whether TSRA-196 can increase the levels of alpha-1 antitrypsin (AAT) in the blood to a normal range and improve its function. To join, you must be between 18 and 70 years old, have a confirmed PiZZ AATD diagnosis, and have low AAT levels. You also need to be a non-smoker. The current recruitment status is unclear.","Participants will be followed for safety and AAT levels for 1 year after treatment.",107,"Participants will receive TSRA-196 through an IV infusion. Safety and AAT levels will be measured for up to 1 year.","Not stated in the trial record.",[32],"v2"]