val-1221 delivered intravenously in ambulatory and ventilator-free participants with late-onset pompe disease

Conditions: Pompe Disease

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)

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.

Eligibility criteria:
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 \ 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

Keywords: gsd-ii pompe disease glycogen storage diseases gaa