This Phase I/II open-label, randomized, dose-escalation study will assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of VAL-1221 versus Myozyme®/Lumizyme® in participants with late-onset glycogen storage disease-II (GSD-II) (Pompe disease)
Part 1 comprises 3 sequential cohorts of 4 patients each randomized to treatment with either VAL-1221 (at 3, 10, or 30 mg/kg) or positive control (rhGAA). Patients randomized to VAL-1221 will receive 7 intravenous (IV) infusions of VAL-1221 (one infusion every other week) over 12 weeks. Control patients will continue receiving their accustomed dose and regimen of Myozyme®. Part 2 is an uncontrolled extension to evaluate long-term effects of VAL-1221 given by IV infusion once every other week at doses up to 40 mg/kg.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
University of California, Irvine
Orange, California, United States
Duke University Medical Center
Durham, North Carolina, United States
National Hospital for Neurology and Neurosurgery
London, United Kingdom
Number of Treatment-related Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline of Study Part 1 though Month 24 of Study Part 2
Number of Participants With Infusion-Associated Reactions to VAL-1221
Time frame: Baseline of Study Part 1 though Month 24 of Study Part 2
Percentage of Participants with Anti-VAL-1221 Antibodies
Time frame: Baseline of Study Part 1 though Month 24 of Study Part 2
Percentage of Participants with GAA Antibodies
Time frame: Baseline of Study Part 1 though Month 24 of Study Part 2
Pharmacokinetics of VAL-1221 in Plasma: Maximum Observed Concentration (Cmax)
Time frame: Part 1: Pre-infusion, end of infusion (EOI) (infusion duration 1 mg/kg/hour), at 0.25, 0.5, 1, 2, 4, 12, 24, 48 and 336 hours after EOI on Days 1, 2, 3 and Week 12; Part 2: Pre-infusion on Weeks 12, 14, 16, 18, 20, 22, Months 12, 24, 36
Pharmacokinetics of VAL-1221 in Plasma: Time to Reach Maximum Concentration (Tmax)
Time frame: Part 1: Pre-infusion, end of infusion (EOI) (infusion duration 1 mg/kg/hour), at 0.25, 0.5, 1, 2, 4, 12, 24, 48 and 336 hours after EOI on Days 1, 2, 3 and Week 12; Part 2: Pre-infusion on Weeks 12, 14, 16, 18, 20, 22, Months 12, 24, 36
Pharmacokinetics of VAL-1221 in Plasma: Area Under the Concentration Time Curve (AUC)
Time frame: Part 1: Pre-infusion, end of infusion (EOI) (infusion duration 1 mg/kg/hour), at 0.25, 0.5, 1, 2, 4, 12, 24, 48 and 336 hours after EOI on Days 1, 2, 3 and Week 12; Part 2: Pre-infusion on Weeks 12, 14, 16, 18, 20, 22, Months 12, 24, 36
Pharmacokinetics of VAL-1221 in Plasma: Terminal Elimination Half-Life ( t1/2)
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Time frame: Part 1: Pre-infusion, end of infusion (EOI) (infusion duration 1 mg/kg/hour), at 0.25, 0.5, 1, 2, 4, 12, 24, 48 and 336 hours after EOI on Days 1, 2, 3 and Week 12; Part 2: Pre-infusion on Weeks 12, 14, 16, 18, 20, 22, Months 12, 24, 36
Pharmacokinetics of VAL-1221 in Plasma: Apparent Total Body Clearance (CL)
Time frame: Part 1: Pre-infusion, end of infusion (EOI) (infusion duration 1 mg/kg/hour), at 0.25, 0.5, 1, 2, 4, 12, 24, 48 and 336 hours after EOI on Days 1, 2, 3 and Week 12; Part 2: Pre-infusion on Weeks 12, 14, 16, 18, 20, 22, Months 12, 24, 36
Pharmacokinetics of VAL-1221 in Plasma: Apparent Volume (V)
Time frame: Part 1: Pre-infusion, end of infusion (EOI) (infusion duration 1 mg/kg/hour), at 0.25, 0.5, 1, 2, 4, 12, 24, 48 and 336 hours after EOI on Days 1, 2, 3 and Week 12; Part 2: Pre-infusion on Weeks 12, 14, 16, 18, 20, 22, Months 12, 24, 36
Change from Baseline in Urinary Hexose Tetrasaccharide (hex4) Excretion at Week 12, Months 6, 9, and 12
Time frame: Baseline of Study Part 1, Week 12 of Study Part 1, Months 12, 24, and 36 of Study Part 2
Change from Baseline in Serum Creatine Kinase (CK) at Week 12, Months 6, 9, and 12
Time frame: Baseline of Study Part 1, Week 12 of Study Part 1, Months 12, 24, and 36 of Study Part 2
Change from Baseline in the Amount of Acid Alpha Glucosidase (GAA) Activity Present in Muscle at Week 12
Time frame: Baseline of Study Part 1, Week 12 of Study Part 1
Change from Baseline in the Muscle Glycogen Content at Week 12
Time frame: Baseline of Study Part 1, Week 12 Study Part 1
Change from Baseline in Creatinine Excretion at Months 6, 9, and 12
Time frame: Baseline of Study Part 1, Months 12, 24, 36 of Study Part 2