A Three-Month, Open-Label, Randomized, Dose-escalation Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of VAL-1221 Versus Myozyme®/Lumizyme® in Patients With Late-Onset GSD-II (Pompe Disease) Followed by Open-Label Treatment With VAL-1221 in All Patients
| Registry | NCT02898753 |
|---|---|
| Status | Terminated - Company closure due to lack of funding |
| Phase | Phase 1 / Phase 2 |
| Study type | Interventional; randomized, parallel, masking: none, treatment |
| Enrollment | 12 (Actual) |
| Sponsor | Valerion Therapeutics, LLC (Industry) |
| Conditions | Pompe Disease |
| Interventions | VAL-1221, RhGAA (Drug) |
| Dates | start 2017-06-21, primary completion 2020-03-25, completion 2020-03-25, first posted 2016-09-13, last updated 2020-06-02 |
| Locations | 3 sites in United States, United Kingdom |
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All trials for Pompe Disease All trials of VAL-1221 All trials of RhGAA
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.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| VAL-1221 3 mg/kg | Experimental | Drug: VAL-1221 | Part 1: Participants will receive VAL-1221 3 mg/kg IV infusion every other week for 12 weeks, inclusive, for a total of 7 infusions. Part 2: Participants from Part 1 of the study who were randomized to VAL-1221 3 mg/kg can enter Part 2 of the study and receive VAL-1221 at a dose of 3 mg/kg IV infusion every other week. The dose can be increased by the Investigator to 10 mg/kg and further to 30 mg/kg (after at least 12 weeks of dosing at 10 mg/kg), depending upon the pharmacodynamics, efficacy, and safety data. |
| VAL-1221 10 mg/kg | Experimental | Drug: VAL-1221 | Part 1: Participants will receive VAL-1221 10 mg/kg IV infusion every other week for 12 weeks, inclusive, for a total of 7 infusions. Part 2: Participants from Part 1 of the study who were randomized to VAL-1221 10 mg/kg can enter Part 2 of the study and receive VAL-1221 at a dose of 10 mg/kg IV infusion every other week. The dose can be increased by the Investigator to 30 mg/kg IV infusion, depending upon the pharmacodynamics, efficacy, and safety data. |
| VAL-1221 30 mg/kg | Experimental | Drug: VAL-1221 | Part 1: Participants will receive VAL-1221 30 mg/kg IV every other week for 12 weeks, inclusive, for a total of 7 infusions. Part 2: Participants from Part 1 of the study who were randomized to VAL-1221 30 mg/kg can enter Part 2 of the study and receive VAL-1221 at a dose of 30 mg/kg IV inufsion every other week. |
| rhGAA | Active comparator | Drug: VAL-1221; Drug: RhGAA | Part 1: Participants will be maintained on their current dose and regimen of Myozyme or Lumizyme. Part 2: Participants from Part 1 of the study who were randomized to rhGAA can enter Part 2 of the study and receive VAL-1221 either 3 mg/kg, 10 mg/kg, or 30 mg/kg (based on the dose of VAL-1221 in respective cohorts to which they were randomized in Part 1) IV infusion every other week. |
Sex: All, ages: 18 Years to any
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
| Facility | City | Country | Status |
|---|---|---|---|
| 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 |