Overview
This is a single-arm, open-label, dose-escalation study to evaluate the safety, tolerability and efficacy of a single intravenous infusion of AB-1009 in adult participants with late-onset Pompe disease (LOPD).
Description
This is an open-label study, up to 12 participants will receive a single IV infusion of AB-1009. Participants will be assigned to either cohort 1 (1.0E13 vg/kg) or Cohort 2 (1.5E13 vg/kg) based on enrollment in the study.
Study duration will include a screening period of up to 75 days, primary observation of 52 weeks, and a long-term follow-up period of 4 years.
Eligibility
Inclusion Criteria:
- Participant must be ≥18 years of age at the time of signing the informed consent form.
- Confirmed GAA enzyme deficiency from any tissue source and/or confirmed biallelic GAA gene mutations.
- Undergone enzyme replacement treatment (ERT) (either alglucosidase alfa (Lumizyme®) or avalglucosidase alfa-ngpt (Nexviazyme®)), for at least 6 months (at least 10 infusions) before signing the initial informed consent form. During the screening process, participants need to remain on their current ERT until close to dosing;
- FVC in the upright position ≥30% and ≤80% of predicted;
- Capable of walking at least 100 meters in the 6MWT (use of a cane, quad cane, or standard walker is permitted);
- Contraceptive/barrier use by men and women requirements as per protocol.
- Capable of giving informed consent and able to understand and comply with all study procedures.
Exclusion Criteria:
- Severe cardiomyopathy, defined as left ventricular ejection fraction (LVEF) \<40% or New York Heart Association (NYHA) functional class 3 or above;
- Require invasive mechanical ventilation, or rely on noninvasive ventilation during the day;
- Intolerance to ERT or investigator-assessed intolerance to ERT, prior experience of serious ERT-related infusion-associated reactions (IARs);
- Have known intrinsic liver diseases, including hepatitis, HIV-related liver disease, prior diagnosis of portal hypertension, splenomegaly, hepatic encephalopathy, severe fatty liver, cirrhosis or liver fibrosis ≥stage 2, ultrasound-identified liver neoplasms, or laboratory tests suggesting elevated alpha-fetoprotein. Patients with liver function tests including ALT or AST \>3× upper limit of normal (ULN) or any total bilirubin above ULN during screening will also be excluded;
- Prior or ongoing medical condition(s), physical finding(s), assessment findings, or laboratory abnormality that, in the investigator's opinion, would impact participant's safety and compliance with the study procedures.
- Have received gene therapy prior to screening;
- Have received any systemic immunosuppressants (except inhalation or topical use) other than glucocorticoids or investigator-recommended immunosuppressants 30 days prior to screening through completion of screening, and/or known intolerance to immunosuppressants such as glucocorticoids;
- Use of investigational drugs or drugs that could affect this study as evaluated by the investigator within 30 days prior to screening through completion of Week 52 or within 5 half-lives of the investigational drug (whichever is longer);
- Have received any vaccine within 30 days prior to dosing;
- Other conditions that make the participant not eligible for the study according to the investigator.