Study ABX1100-1001 is a first-in-human (FIH), phase 1 study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of a single ascending dose (SAD) and multiple doses (MD) of ABX1100 administered intravenously to healthy participants and patients with LOPD. * Part A features a SAD study with a double-blind, placebo-controlled, randomized design in NHVs involving 3 cohorts (A1-A3). This Part also includes a single dose, open-labeled cohort (A4) in NHVs which will commence after cohorts A1-3. * Part B is a MD, double-blind, placebo-controlled, randomized design in NHVs. The MD Part B will commence after completion of Cohorts A1, A2 and A3 in the SAD Part A and SRC review of these 3 cohorts. * Part C opened for enrollment after the Safety Review Committee (SRC) review of safety, PK and PD data from both Part A and Part B. Part C is a MD, open-label design in patients with Late-Onset Pompe Disease.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
46
Centyrin protein-siRNA conjugate
placebo saline injection
UCI
Orange, California, United States
Washington University School of Medicine
St Louis, Missouri, United States
Lysosomal and Rare Disorders Research and Treatment Center, Inc
Fairfax, Virginia, United States
MAGIC clinic
Calgary, Alberta, Canada
McMaster University
Hamilton, Ontario, Canada
Number of subjects with treatment-emergent adverse events (TEAEs)
Adverse Events will be graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Adverse events (AEs) will be reported based on clinical laboratory tests, vital signs, physical examinations, electrocardiograms, and echocardiograms from the time informed consent is signed through 8 weeks after ABX1100 administration for Part A and through 12 weeks after ABX1100 administration for Part B, and up to 20 weeks for Part C. AEs will be considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Time frame: up to 20 weeks
Plasma pharmacokinetics as measured by Cmax
Plasma samples will be taken pre-dose, 10 min, end of infusion, 0.5, 1, 3, 6 and 8 hours after the start of ABX1100 administration
Time frame: 0-8 hours after ABX1100 administration
Plasma pharmacokinetics as measured by Tmax
Plasma samples will be taken pre-dose, 10 min, end of infusion, 0.5, 1, 3, 6 and 8 hours after the start of ABX1100 administration
Time frame: 0-8 hours after ABX1100 administration
Plasma pharmacokinetics as measured by AUC
Plasma samples will be taken pre-dose, 10 min, end of infusion, 0.5, 1, 3, 6 and 8 hours after the start of ABX1100 administration
Time frame: 0-8 hours after ABX1100 administration
Immunogenicity of AXB1100 as measured by anti-ABX1100 antibodies in serum
Plasma samples will be taken pre-dose, Day 15 and Day 29 after ABX1100 administration (Part A); Plasma samples will be taken pre-dose, Day 15, Day 29, Day 43, Day 57 and Day 71 after ABX1100 administration (Part B); Plasma samples will be taken pre-dose, Day 15, Day 29, Day 43, Day 57 and Day 71 after ABX1100 administration; D113 blood draw for ADA may be requested by Sponsor based on results of earlier timepoints. (Part C);
Time frame: Up to 16 weeks
Muscle drug concentration
Concentration of siRNA component in skeletal muscle
Time frame: Needle muscle biopsies at pre-dose, week 10 and week 6 or 16
Pharmacodynamics as measured by GYS1 mRNA in muscle
Change in GYS1 mRNA from pre-dose
Time frame: Needle muscle biopsies at pre-dose, week 10 and week 6 or 16
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