A Study of KB408 for the Treatment of Alpha-1 Antitrypsin Deficiency
ConditionAlpha 1-Antitrypsin Deficiency
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-70
SponsorKrystal Biotech, Inc.
About this trial
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.
Eligibility criteria
Qualifiers
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.
Subject is aged ≥18 to ≤70 years, at the time of informed consent.
Subject has a genetically confirmed diagnosis of AATD with a PI*ZZ or PI*ZNull genotype.
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.
Disqualifiers
Pulmonary function test with percent predicted forced expired volume in 1 second (ppFEV1) after inhalation of a bronchodilator is <40% at Screening.
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).
Known ongoing or history of clinically significant pulmonary impairment other than AATD.
A pulmonary exacerbation within six weeks (42 days) of first dose.
Trial design
Treatments tested in this trial
- KB408 (Nebulization)
Treatment groups
15 Participants
are divided into 4 treatment groupsSponsors and collaborators
Source ClinicalTrials.gov