A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of DNL952 in Adult Participants With Late-Onset Pompe Disease

A Phase 1, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL952 in Adult Participants With Late-Onset Pompe Disease

This is a Phase 1, multicenter, open-label study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DNL952 in adult participants with late-onset Pompe disease. The principal aim of this study is to obtain safety and tolerability data across varous dose levels of DNL952 in participants with late-onset Pompe disease (LOPD).

Key Inclusion Criteria:

• Body weight ≥40 kg
• Diagnosis of LOPD
• Upright FVC ≥ 30% of predicted normal value
• Able to ambulate ≥ 40 meters (use of assistive devices is acceptable)
• [Cohorts A1-A4 only] Have received avalglucosidase alfa or cipaglucosidase alfa at a dose of 20 mg/kg every 2 weeks for at least 12 months prior to screening
• [Cohorts B1-B2 only] Must not have received any enzyme-replacement therapy for Pompe disease in the 12 months prior to screening

Key Exclusion Criteria:

• Any ongoing, clinically significant, unstable, or poorly controlled neurological, psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematological, immunological, allergic, or ophthalmic disease not related to Pompe disease, or other major disorders. Well-controlled conditions are permitted if investigator and Sponsor agree.
• Wheelchair-dependent
• Require noninvasive ventilation for an average of more than 6 hours per day while awake or any invasive ventilation. Use of noninvasive ventilation during sleep is acceptable.
• Received an experimental gene therapy at any time or participation in any other investigational drug trial or use of investigational drug within 60 days or 5 half-lives, whichever is longer, before screening