Pompe Disease
Conditions
Keywords
GSD-II, Pompe Disease, Glycogen Storage Diseases, GAA
Brief summary
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)
Detailed description
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.
Interventions
Sponsors
Valerion Therapeutics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant is able and willing to provide informed consent prior to any study procedures are performed * Diagnosis of GSDII based on one of the following: * Endogenous cultured skin fibroblast GAA activity less than (\<) 40 percent (%) of adult normal level * Endogenous whole blood or dried blood spot GAA activity in deficiency range * Genetic analysis showing pathogenic variants in both alleles * Onset of Pompe disease-related symptoms after 1 year of age * Previously treated with Myozyme or Lumizyme for at least 12 months and on a stable regimen for the past 6 months * Sexually active participants who are willing to use an acceptable method of contraception (abstinence, oral contraceptives, barrier method with spermicide, surgical sterilization, implanted or injectable contraceptives with a stable dose for at least 1 month prior to Baseline, hormonal intra-uterine device \[IUD\] inserted at least 1 month prior to Baseline) during the study and for 30 days after completion of treatment * If participant is female and not considered to be of childbearing potential, she is at least 2 years post-menopause, has undergone a tubal ligation, a total hysterectomy or bilateral oophorectomy * If participant is female and of childbearing potential, she has a negative serum pregnancy test during screening and Baseline and must be willing to undergo pregnancy testing at specific intervals during the study * Participant meets at least one of the following criteria: greater than (\>) 30% and \<80% predicted upright forced volume capacity (FVC) or participant is able to walk \>20% but \<80% predicted normal on 6-minute walk test with or without use of assistive devices * Able to comply with protocol requirements
Exclusion criteria
* Cardiac involvement in first year of life * Anti-GAA antibody titers \>1:51,200 at two time points * Prior use of chaperone therapy for GSD-II within the last 12 months * Use of immunosuppressive medication other than glucocorticoids within 6 months prior to study enrollment * Use of invasive ventilatory assistance other than Bilevel Positive Airway Pressure (BiPAP) at night or during periods of rest * Has received any investigational medication or has enrolled in any study involving investigational drugs or therapies within 30 days prior to first dose of study drug * Start of or change in usual regimen of albuterol or respiratory muscle training within 30 days prior to first dose of study drug * History of sensitivity to any of the constituents of the study drug * Participant is breastfeeding or planning to become pregnant or to breastfeed during the study or is currently breastfeeding * Participant has a medical condition or circumstance that, in the opinion of the investigator, might compromise the participant's ability to comply with the protocol or the participant's well-being or safety * Participant has any condition that, in the view of the investigator, places the participant at high risk of poor treatment compliance or of not completing the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Treatment-related Treatment-emergent Adverse Events (TEAEs) | Baseline of Study Part 1 though Month 24 of Study Part 2 |
| Number of Participants With Infusion-Associated Reactions to VAL-1221 | Baseline of Study Part 1 though Month 24 of Study Part 2 |
| Percentage of Participants with Anti-VAL-1221 Antibodies | Baseline of Study Part 1 though Month 24 of Study Part 2 |
| Percentage of Participants with GAA Antibodies | Baseline of Study Part 1 though Month 24 of Study Part 2 |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics of VAL-1221 in Plasma: Apparent Total Body Clearance (CL) | 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) | 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 | Baseline of Study Part 1, Week 12 of Study Part 1, Months 12, 24, and 36 of Study Part 2 |
| Pharmacokinetics of VAL-1221 in Plasma: Maximum Observed Concentration (Cmax) | 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 the Amount of Acid Alpha Glucosidase (GAA) Activity Present in Muscle at Week 12 | Baseline of Study Part 1, Week 12 of Study Part 1 |
| Change from Baseline in the Muscle Glycogen Content at Week 12 | Baseline of Study Part 1, Week 12 Study Part 1 |
| Change from Baseline in Creatinine Excretion at Months 6, 9, and 12 | Baseline of Study Part 1, Months 12, 24, 36 of Study Part 2 |
| Change from Baseline in Serum Creatine Kinase (CK) at Week 12, Months 6, 9, and 12 | Baseline of Study Part 1, Week 12 of Study Part 1, Months 12, 24, and 36 of Study Part 2 |
| Pharmacokinetics of VAL-1221 in Plasma: Time to Reach Maximum Concentration (Tmax) | 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) | 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) | 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 |
Countries
United Kingdom, United States
Outcome results
None listed