DNL952 treatment for adults 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 Phase 1 trial will test DNL952 in adults with late-onset Pompe disease to see if it is safe and how the drug is handled by the body.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Denali Therapeutics Inc. (Industry-sponsored)
• Locations: 1 site (Fairfax, Virginia)
• Trial ID: NCT07354724 on ClinicalTrials.gov

What this trial studies

This is an open-label, multicenter Phase 1 dose-ranging study enrolling adults with late-onset Pompe disease to collect safety, tolerability, pharmacokinetic, and pharmacodynamic data for DNL952. Participants are grouped into cohorts with differing prior enzyme-replacement therapy histories and will receive DNL952 at escalating dose levels. Key entry requirements include a confirmed LOPD diagnosis, minimum body weight, upright FVC ≥30% predicted, and the ability to ambulate at least 40 meters. Major exclusions include wheelchair dependence, need for noninvasive ventilation more than 6 hours per day while awake, or other unstable major medical conditions not related to Pompe disease.

Who should consider this trial

Good fit: Adults with confirmed late-onset Pompe disease who weigh ≥40 kg, can walk at least 40 meters, have upright FVC ≥30% predicted, and meet the cohort-specific enzyme-replacement therapy history are the intended participants.

Not a fit: Patients who are wheelchair-dependent, require noninvasive ventilation for more than 6 hours per day while awake, have unstable major medical conditions unrelated to Pompe disease, or do not meet cohort-specific prior ERT criteria are unlikely to benefit from participation in this early-phase safety study.

Why it matters

Potential benefit: If DNL952 is safe and shows favorable PK/PD, it could advance into later testing and potentially become a new option to help preserve breathing and muscle function in adults with late-onset Pompe disease.

How similar studies have performed: Approved enzyme-replacement therapies such as avalglucosidase alfa and cipaglucosidase alfa have helped many patients with Pompe disease, but DNL952 is an investigational agent in early human testing with limited prior clinical data.

Eligibility 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

Where this trial is running

Fairfax, Virginia

• The Lysosomal & Rare Disorders Research & Treatment Center — Fairfax, Virginia, United States (Recruiting)

Conditions Late-onset Pompe Disease; LOPD; Pompe; acid maltase deficiency; glycogen storage disease type II; ERT; enzyme replacement therapy