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

Denali Therapeutics

Status and phase: Begins enrollment this month; Phase 1

Conditions: Late-onset Pompe Disease

Treatments: Drug: DNL952

Study type: Interventional

Funder types: Industry

Identifiers

NCT07354724

DNLI-J-0001

2025-524082-25-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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).

Enrollment: 32 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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32 participants in 6 patient groups

Cohort A1

Experimental group

Description:

Participants with LOPD

Treatment:

Drug: DNL952

Cohort A2

Experimental group

Description:

Participants with LOPD

Treatment:

Drug: DNL952

Cohort A3 (Optional)

Experimental group

Description:

Participants with LOPD

Treatment:

Drug: DNL952

Cohort A4 (Optional)

Experimental group

Description:

Participants with LOPD

Treatment:

Drug: DNL952

Cohort B1 (Optional)

Experimental group

Description:

Participants with LOPD

Treatment:

Drug: DNL952

Cohort B2 (Optional)

Experimental group

Description:

Participants with LOPD

Treatment:

Drug: DNL952