[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT06049082":3,"trial-entities:NCT06049082":133,"trial-summary:NCT06049082":138},{"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":25,"interventions":28,"primary_outcomes":38,"secondary_outcomes":43,"sex":56,"minimum_age":57,"maximum_age":58,"healthy_volunteers":15,"eligibility_criteria":59,"std_ages":70,"locations":73,"central_contacts":119,"overall_officials":127,"references":131,"see_also_links":132},"NCT06049082","KB408-01","A Study of KB408 for the Treatment of Alpha-1 Antitrypsin Deficiency","A Phase 1 Study of Inhaled KB408 for the Treatment of Alpha-1 Antitrypsin Deficiency","RECRUITING","2026-12","2025-07","2025-07-22","2024-02-15","Krystal Biotech, Inc.","INDUSTRY",false,"The Sponsor is developing KB408, a replication-defective, non-integrating herpes simplex virus type 1 (HSV-1)-derived vector engineered to deliver functional full-length human SERPINA1 to the airways of people with alpha-1 antitrypsin deficiency (AATD) via nebulization. This study is designed to evaluate safety and pharmacodynamics of KB408 in adults with AATD with a PI\\*ZZ or PI\\*ZNull genotype. Three planned dose levels of KB408 will be evaluated in single dose escalation cohorts. Repeat dosing will be evaluated at the mid dose level. Subjects taking intravenous AAT augmentation therapy are not required to wash out from IV AAT in the low and mid dose cohorts. In the repeat dose and the high dose cohorts, subjects must wash out from IV AAT for at least 10 days, as applicable.",null,[19],"Alpha 1-Antitrypsin Deficiency",[],"INTERVENTIONAL","TREATMENT",[24],"PHASE1",{"count":26,"type":27},15,"ESTIMATED",[29],{"type":30,"name":31,"description":32,"armGroupLabels":33},"DRUG","KB408 (Nebulization)","Nebulized solution of KB408, a replication-defective HSV-1 vector expressing full length human SERPINA1",[34,35,36,37],"Cohort 1: Low dose KB408","Cohort 2: Mid dose KB408","Cohort 2b: Mid dose KB408","Cohort 3: High dose KB408",[39],{"measure":40,"description":41,"timeFrame":42},"To evaluate safety and tolerability of KB408 based upon assessment of adverse events (frequency, severity, relatedness), and changes from baseline in vital signs, ECG, spirometry, and clinical laboratory test results","Number of subjects with treatment related adverse events as assessed by NCI-CTCAE v5","2 months (Cohorts 1, 2, 3); 3 months (Cohort 2b)",[44,47,50,53],{"measure":45,"description":46,"timeFrame":42},"To assess the effect of KB408 on serum alpha-1 antitrypsin (AAT) concentration","Change from baseline in serum AAT levels",{"measure":48,"description":49,"timeFrame":42},"To assess the effect of KB408 on plasma neutrophil elastase (NE) concentration","Change from baseline in plasma NE levels",{"measure":51,"description":52,"timeFrame":42},"To evaluate the effect of KB408 on AAT concentration in the lung","Change from baseline in AAT levels in bronchoalveolar lavage fluid",{"measure":54,"description":55,"timeFrame":42},"To evaluate the effect of KB408 on NE concentration in the lung","Change from baseline in NE levels in bronchoalveolar lavage fluid","ALL","18 Years","70 Years",{"inclusion":60,"exclusion":61,"raw_text":69},[],[62,63,64,65,66,67,68],"Platelet count \\\u003C100×10\\^9\u002FL","Hemoglobin \\\u003C9 g\u002FdL","White blood cell count \\\u003C3 or \\>15×10\\^9\u002FL","Sodium \\\u003C130 or \\>150 mmol\u002FL","Potassium \\\u003C3 or \\>5.5 mmol\u002FL","Carbon dioxide \\\u003C16 mmol\u002FL","Creatinine \\>2 mg\u002FdL 15. Subject is known to be noncompliant or is unlikely to comply with the requirements of the study protocol, in the opinion of the Investigator. 16. Females who are pregnant or nursing. 17. Subject who is unwilling to comply with contraception requirements per protocol","Inclusion Criteria:\n\n1. The subject or legally authorized representative must have read, understood, and signed an Institutional Review Board (IRB) approved Informed Consent Form and must be willing and able to comply with study procedures and instructions.\n2. Subject is aged ≥18 to ≤70 years, at the time of informed consent.\n3. Subject has a genetically confirmed diagnosis of AATD with a PI\\*ZZ or PI\\*ZNull genotype.\n4. Cohort 2b and Cohort 3: Subjects receiving AAT augmentation therapy must be willing to washout for at least 10 days prior to Screening and be willing to remain off augmentation therapy for the duration of the study.\n5. Cohort 2b and Cohort 3: Serum AAT level \\\u003C11 μM at Screening.\n6. Willing to remain on a stable regimen of treatment during the study.\n7. Resting oxygen saturation ≥92% on room air at Screening.\n8. Clinically stable and in good general health, except for AATD, as determined by the Investigator.\n\nExclusion Criteria:\n\n1. Pulmonary function test with percent predicted forced expired volume in 1 second (ppFEV1) after inhalation of a bronchodilator is \\\u003C40% at Screening.\n2. Diffusing capacity of the lungs for carbon monoxide (DLCO) \\\u003C30 percent predicted (historical DLCO within 2 years prior to Screening without any intervening change in clinical status since the measurement was taken, or as measured at Screening).\n3. Known ongoing or history of clinically significant pulmonary impairment other than AATD.\n4. A pulmonary exacerbation within six weeks (42 days) of first dose.\n5. Initiation of any new chronic therapy or any change in ongoing therapy routine within 28 days of first dose.\n6. Participation in another interventional clinical study or treatment with an investigational agent within 30 days or 5 half-lives, whichever is longer, of first dose. Previous treatment with a genetic therapy for AATD, where the investigational product was demonstrated to be non-efficacious, is not exclusionary.\n7. History of or listed for solid organ transplantation or has undergone major lung surgery (e.g., lobectomy) within 6 months of first dose.\n8. Any clinical condition or illness (including a history or current evidence of substance abuse or dependence) that, in the opinion of the Investigator, would impact a subject's ability to complete all study-related procedures and\u002For poses an additional risk to the assessment of safety of KB408.\n9. An active oral herpes infection 30 days prior to the first dose.\n10. Clinically significant hepatic dysfunction defined as any one of the following:\n\n    1. AST and ALT ≥3× upper limit of normal (ULN) at Screening\n    2. Total bilirubin ≥2× ULN at Screening (unless associated with Gilbert's syndrome)\n    3. Evidence of liver cirrhosis with clinical manifestations of portal hypertension (e.g., ascites, encephalopathy, variceal hemorrhage)\n11. History of cigarette smoking or any other tobacco use, or use of e-cigarettes or other recreational inhalant, within 6 months of Screening.\n12. Unwilling to refrain from smoking, e-cigarette use, or vaping throughout the duration of the study.\n13. A positive urine cotinine result that is consistent with active smoking at Screening. (A positive cotinine test due to nicotine replacement therapy for the purpose of smoking cessation, as attested by the Investigator, is allowed.)\n14. Abnormal hematology or chemistry testing at Screening as defined below, or any other clinically significant abnormalities that the Investigator believes may interfere with the assessment of safety of the study treatment.\n\n    * Platelet count \\\u003C100×10\\^9\u002FL\n    * Hemoglobin \\\u003C9 g\u002FdL\n    * White blood cell count \\\u003C3 or \\>15×10\\^9\u002FL\n    * Sodium \\\u003C130 or \\>150 mmol\u002FL\n    * Potassium \\\u003C3 or \\>5.5 mmol\u002FL\n    * Carbon dioxide \\\u003C16 mmol\u002FL\n    * Creatinine \\>2 mg\u002FdL\n15. Subject is known to be noncompliant or is unlikely to comply with the requirements of the study protocol, in the opinion of the Investigator.\n16. Females who are pregnant or nursing.\n17. Subject who is unwilling to comply with contraception requirements per protocol",[71,72],"ADULT","OLDER_ADULT",[74,92,104],{"facility":75,"status":8,"city":76,"state":77,"zip":78,"country":79,"contacts":80,"geoPoint":89},"University of Florida, Gainesville","Gainesville","Florida","32610","United States",[81,86],{"name":82,"role":83,"phone":84,"email":85},"Allison Faunce","CONTACT","352-273-8666","Allison.Faunce@medicine.ufl.edu",{"name":87,"role":88},"Jorge Lascano, MD","PRINCIPAL_INVESTIGATOR",{"lat":90,"lon":91},29.65163,-82.32483,{"facility":93,"status":8,"city":94,"state":95,"zip":96,"country":79,"contacts":97,"geoPoint":101},"Medical University of South Carolina","Charleston","South Carolina","29425",[98,100],{"name":99,"role":83},"Charlton Strange, MD",{"name":99,"role":88},{"lat":102,"lon":103},32.77632,-79.93275,{"facility":105,"status":8,"city":106,"state":107,"zip":108,"country":79,"contacts":109,"geoPoint":116},"Renovatio Clinical","The Woodlands","Texas","77380",[110,114],{"name":111,"role":83,"phone":112,"email":113},"Dustyn Tobin","713-703-2398","dustyn.tobin@renovatioclinical.com",{"name":115,"role":88},"Ather J Siddiqi, MD",{"lat":117,"lon":118},30.15799,-95.48938,[120,124],{"name":121,"role":83,"phone":122,"email":123},"David Sweet, MD, PhD","412-586-5830","dsweet@krystalbio.com",{"name":125,"role":83,"phone":122,"email":126},"Brittani Agostini, RN, CCRC","bagostini@krystalbio.com",[128],{"name":121,"affiliation":129,"role":130},"Director of Clinical Development","STUDY_DIRECTOR",[],[],{"nct_id":4,"conditions":134,"biomarkers":136},[135],"Alpha-1 Antitrypsin Deficiency",[137],"SERPINA1 Gene",{"nct_id":4,"found":139,"summary":140,"prompt_version":150},true,{"design":141,"status":142,"heading":143,"summary":144,"follow_up":145,"word_count":146,"commitments":147,"compensation":148,"drugs_mentioned":149},"This is an interventional study, meaning participants will receive a specific treatment. It plans to enroll 15 participants to test different dose levels of KB408.","completed","A Study of KB408 for Alpha-1 Antitrypsin Deficiency","This study is looking into KB408, a new treatment for Alpha-1 Antitrypsin Deficiency (AATD). KB408 is given through a nebulizer (a device that turns liquid medicine into a mist you can breathe in). The main goal of this study is to check the safety of KB408 and how well people tolerate it. Researchers will look at side effects, vital signs, heart activity (ECG), lung function (spirometry), and blood tests over 2 or 3 months. You may be able to join if you are 18 to 70 years old and have AATD with a PI*ZZ or PI*ZNull genotype. The study plans to enroll 15 participants. The current status of this study is unclear.","Safety and tolerability will be assessed for 2 months (for Cohorts 1, 2, 3) or 3 months (for Cohort 2b) after treatment.",112,"Not specified in the trial record.","Not stated in the trial record.",[],"v2"]