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).

Study Overview

• Status: Recruiting
• Conditions: Late-onset Pompe Disease
• Intervention / Treatment: Drug: DNL952

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials at Denali Therapeutics; Phone Number: Email:; Email: clinical-trials@dnli.com

Study Locations

• United States
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Recruiting
      • The Lysosomal & Rare Disorders Research & Treatment Center
      • Contact: Study Coordinator; Phone Number: 571-732-4575; Email: aagha@ldrtc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A1; Participants with LOPD	Drug: DNL952; Intravenous repeating dose
Experimental: Cohort A2; Participants with LOPD	Drug: DNL952; Intravenous repeating dose
Experimental: Cohort A3 (Optional); Participants with LOPD	Drug: DNL952; Intravenous repeating dose
Experimental: Cohort A4 (Optional); Participants with LOPD	Drug: DNL952; Intravenous repeating dose
Experimental: Cohort B1 (Optional); Participants with LOPD	Drug: DNL952; Intravenous repeating dose
Experimental: Cohort B2 (Optional); Participants with LOPD	Drug: DNL952; Intravenous repeating dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence, severity, and seriousness of treatment-emergent adverse events (TEAEs)	48 weeks
Incidence and severity of infusion-related reacations (IRRs)	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameter: Maximum concentration (Cmax) of DNL952 in serum		48 weeks
PK Parameter: Time to reach maximum concentration (tmax) of DNL952 in serum		48 weeks
PK Parameter: Area under the concentration-time curve (AUC) from time zero to time of last measurable concentration (AUClast) of DNL952 in serum		48 weeks
PK Parameter: AUC from time 0 to infinity (AUC∞) of DNL952 in serum	single dose only	48 weeks
PK parameter: AUC from time zero to time t (AUCt) of DNL952 in serum	multiple doses only	48 weeks
PK Parameter: terminal elimination half-life (t1/2) of DNL952 in serum		48 weeks

Collaborators and Investigators

• Sponsor: Denali Therapeutics Inc.
• Investigators: Study Director: Medical Monitor, Denali Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: January 12, 2026
• First Submitted That Met QC Criteria: January 12, 2026
• First Posted (Actual): January 21, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: enzyme replacement therapy; ERT; LOPD; Pompe; acid maltase deficiency; glycogen storage disease type II
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lysosomal Storage Diseases, Nervous System; Glycogen Storage Disease; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Glycogen Storage Disease Type II
• Other Study ID Numbers: DNLI-J-0001; 2025-524082-25-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No