This is an open-label, single-arm, dose-escalation trial to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of RAG-18 in pediatric patients with Duchenne Muscular Dystrophy (DMD). The study will enroll approximately 12 subjects into four cohorts to assess the safety and tolerability of ascending intravenous doses. Secondary objectives include characterizing the pharmacokinetics (PK)/pharmacodynamics (PD) profile and assessing exploratory efficacy through changes in muscle biomarkers, muscle composition, cardiac/pulmonary function, and motor performance. The decision to escalate to the next dose level will be based on a comprehensive safety evaluation of the preceding cohort.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
RAG-18 is a therapeutic small activating RNA (saRNA) duplex molecule comprised of two partially chemically modified complementary oligonucleotide strands
Peking Union Medical College Hospital
Beijing, China
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
To evaluate the safety profile of RAG-18 by recording the frequency, nature, and severity of all adverse events and serious adverse events observed during the study. The relationship of these events to the study drug will be assessed.
Time frame: From Baseline up to the end of the study (Day 169)
Maximum Observed Plasma Concentration (Cmax) of RAG-18
To evaluate the pharmacokinetic profile of RAG-18 after intravenous infusion.
Time frame: Day 1 and Day 85 (assessed at pre-dose, and multiple timepoints up to 168 hours post-dose)
Time to Maximum Observed Plasma Concentration (Tmax) of RAG-18
To determine the time to reach the maximum observed plasma concentration of RAG-18.
Time frame: Day 1 and Day 85 (PK samples collected at pre-dose and multiple timepoints up to 168 hours post-dose)
Area Under the Plasma Concentration-Time Curve (AUC) of RAG-18
To determine the total drug exposure over time by calculating the Area Under the Plasma Concentration-Time Curve (AUC).
Time frame: Day 1 and Day 85 (PK samples collected at pre-dose and multiple timepoints up to 168 hours post-dose)
Terminal Half-Life (t1/2) of RAG-18
To determine the terminal elimination half-life of RAG-18 in plasma.
Time frame: Day 1 and Day 85 (PK samples collected at pre-dose and multiple timepoints up to 168 hours post-dose)
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