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
This trial does not accept healthy volunteersQualifiers
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
Design model
Single group
Treatments tested in this trial
KB408 (Nebulization)
DrugNebulized solution of KB408, a replication-defective HSV-1 vector expressing full length human SERPINA1
Treatment groups
15 Participants
are divided into 4 treatment groupsGroup A: Cohort 1: Low dose KB408Experimental treatment 1 intervention
Group B: Cohort 2: Mid dose KB408Experimental treatment 1 intervention
Group C: Cohort 3: High dose KB408Experimental treatment 1 intervention
Group D: Cohort 2b: Mid dose KB408Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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
Time frame
2 months (Cohorts 1, 2, 3); 3 months (Cohort 2b)Secondary outcomes
1
To assess the effect of KB408 on serum alpha-1 antitrypsin (AAT) concentration
Change from baseline in serum AAT levels
Time frame
2 months (Cohorts 1, 2, 3); 3 months (Cohort 2b)2
To assess the effect of KB408 on plasma neutrophil elastase (NE) concentration
Change from baseline in plasma NE levels
Time frame
2 months (Cohorts 1, 2, 3); 3 months (Cohort 2b)3
To evaluate the effect of KB408 on AAT concentration in the lung
Change from baseline in AAT levels in bronchoalveolar lavage fluid
Time frame
2 months (Cohorts 1, 2, 3); 3 months (Cohort 2b)4
To evaluate the effect of KB408 on NE concentration in the lung
Change from baseline in NE levels in bronchoalveolar lavage fluid
Time frame
2 months (Cohorts 1, 2, 3); 3 months (Cohort 2b)Sponsors and contacts
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Source ClinicalTrials.gov