Netherton syndrome (NS) is a rare autosomal recessive disease and no systemic treatment or standard of care currently exists for patients with NS. DS-2325a, a specific and potent inhibitor of kallikrein 5, is expected to treat NS by replacing a defective gene.
This study for DS-2325a will evaluate the safety, tolerability, and pharmacokinetics of multiple ascending doses of DS-2325a in healthy participants. DS-2325a will be evaluated after subcutaneous (SC) injections.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
24
Quotient Sciences -Miami
Miami, Florida, United States
Number of Participants with Any Treatment-emergent Adverse Events Following Administration of DS-2325a
Treatment-emergent adverse events (TEAEs) are defined as new adverse events (AEs) that occur after the dose of study drug or as AEs that were present prior to the dose of study drug but which worsened in severity after the start of study drug.
Time frame: Screening (Day -28 to -3) pre-dose up to Day 78 post-dose
Pharmacokinetic Parameter Area Under the Concentration Curve (AUCtau)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Time frame: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Pharmacokinetic Parameter Maximum Concentration (Cmax)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Time frame: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Pharmacokinetic Parameter Average Concentration (Cavg)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Time frame: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Pharmacokinetic Parameter Drug Accumulation Ratio for AUCtau and Cmax (Rac)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Time frame: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
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Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Time frame: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Pharmacokinetic Parameter Terminal Elimination Half-life (T1/2)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Time frame: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Pharmacokinetic Parameter Elimination Rate Constant Associated With the Terminal Phase (Kel)
Pharmacokinetic parameters will be calculated for DS-2325a by noncompartmental methods.
Time frame: Day 1: pre-dose & 4, 8, 24, 72, 96, 120, 144 hours (hr) post-dose; Day 8 & 14: pre-dose; Day 22: pre-dose & 4, 8, 24, 48, 72, 96, 120, 144, 168 hr post-dose; Day 36, 43, 57, & 78
Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)
Blood samples will be collected to determine ADAs.
Time frame: Day 1: pre-dose and Days 15, 22, 36, 57, and 78