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Clinical Trial Report
Gene Therapy Trial Report
Summary
A Study of KB408 for the Treatment of Alpha-1 Antitrypsin Deficiency
NCTID
NCT06049082
(View at clinicaltrials.gov)
Description
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. Subjects taking intravenous AAT augmentation therapy are not required to wash out from IV AAT in the low and mid dose cohorts. At the high dose, two cohorts will be conducted in parallel to evaluate patients on and off IV augmentation therapy.
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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
Recruiting
Enrollment Count
12
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
Dose 4
Dose 5
Study Record Dates
Current Stage
Phase1
Submit Date
2023-09-15
Completion Date
2026-05
Last Update
2024-12-16
Participation Criteria
Eligible Age
18 Years - 70 Years
Standard Ages
Adult, Older adult
Sexes Eligible for Study
ALL
Locations
No.of Trial Sites
2
Locations
United States
Regulatory Information
Has US IND
True
FDA Designations
Orphan Drug Designation
Recent Updates
Company expects additional updates in 2025, will open cohort 3 (highest dose)
Resources/Links
News and Press Releases
(Corporate Presentation) Genetic Medicines for High Unmet Medical Needs - May 2024
Krystal Biotech Announces Initial Clinical Update for Rare Respiratory Disease Programs KB408 and KB407 Including Early Clinical Evidence of Gene Delivery to the Lung of AATD Patients and Increase in Lung AAT to Therapeutic Levels
Preclinical Publications
(Poster) Nonclinical pharmacology of KB408, an HSV-1-based vector designed for the treatment of alpha-1 antitrypsin deficiency, in the SERPINA1 knockout mouse model - ESGCT 2023
(Poster) Murine Toxicology Study of Repeat-Dose Inhaled KB408, an HSV-1-Based Vector for the Treatment of Alpha-1 Antitrypsin Deficiency - ATS 2024