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Gene Therapy Trial Report

Summary

A Study of KB408 for the Treatment of Alpha-1 Antitrypsin Deficiency


NCTID NCT06049082 (View at clinicaltrials.gov)
Description
Development Status Active
Indication Alpha-1 Antitrypsin Deficiency (AATD)
Disease Ontology Term DOID:13372
Compound Name KB-408
Sponsor Krystal Biotech, Inc.
Funder Type Industry
Recruitment Status
Enrollment Count 15 (ESTIMATED)
Results Posted Not Available

Therapy Information


Target Gene/Variant SERPINA1
Therapy Type Gene transfer
Therapy Route In-vivo
Mechanism of Action Functional gene replacement
Route of Administration Inhalational
Drug Product Type Viral vector
Target Tissue/Cell Lung
Delivery System Viral transduction
Vector Type HSV-1
Editor Type none
Dose 1 10^9 PFU
Dose 2 10^10 PFU
Dose 3 10^11 PFU

Study Record Dates


Current Stage Phase1
Submit Date 2023-09-15
Completion Date 2026-12
Last Update 2025-07-22

Participation Criteria


Eligible Age 18 Years - 70 Years
Standard Ages Adult, Older adult
Sexes Eligible for Study ALL
Eligibility Criteria
Inclusion Criteria: 1. 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. 2. Subject is aged ≥18 to ≤70 years, at the time of informed consent. 3. Subject has a genetically confirmed diagnosis of AATD with a PI\*ZZ or PI\*ZNull genotype. 4. 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. 5. Cohort 2b and Cohort 3: Serum AAT level \<11 μM at Screening. 6. Willing to remain on a stable regimen of treatment during the study. 7. Resting oxygen saturation ≥92% on room air at Screening. 8. Clinically stable and in good general health, except for AATD, as determined by the Investigator. Exclusion Criteria: 1. Pulmonary function test with percent predicted forced expired volume in 1 second (ppFEV1) after inhalation of a bronchodilator is \<40% at Screening. 2. Diffusing capacity of the lungs for carbon monoxide (DLCO) \<30 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). 3. Known ongoing or history of clinically significant pulmonary impairment other than AATD. 4. A pulmonary exacerbation within six weeks (42 days) of first dose. 5. Initiation of any new chronic therapy or any change in ongoing therapy routine within 28 days of first dose. 6. 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. 7. History of or listed for solid organ transplantation or has undergone major lung surgery (e.g., lobectomy) within 6 months of first dose. 8. 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/or poses an additional risk to the assessment of safety of KB408. 9. An active oral herpes infection 30 days prior to the first dose. 10. Clinically significant hepatic dysfunction defined as any one of the following: 1. AST and ALT ≥3× upper limit of normal (ULN) at Screening 2. Total bilirubin ≥2× ULN at Screening (unless associated with Gilbert's syndrome) 3. Evidence of liver cirrhosis with clinical manifestations of portal hypertension (e.g., ascites, encephalopathy, variceal hemorrhage) 11. History of cigarette smoking or any other tobacco use, or use of e-cigarettes or other recreational inhalant, within 6 months of Screening. 12. Unwilling to refrain from smoking, e-cigarette use, or vaping throughout the duration of the study. 13. 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.) 14. 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. * Platelet count \<100×10\^9/L * Hemoglobin \<9 g/dL * White blood cell count \<3 or \>15×10\^9/L * Sodium \<130 or \>150 mmol/L * Potassium \<3 or \>5.5 mmol/L * Carbon dioxide \<16 mmol/L * Creatinine \>2 mg/dL 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
View Inclusion and Exclusion Criteria at ClinicalTrials.gov

Locations


No.of Trial Sites 3
Locations United States

Regulatory Information


Has US IND True
FDA Designations Orphan Drug Designation
Recent Updates Interim data expected in 1H 2026

Resources/Links