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

Purpose

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).

Condition

  • Late-onset Pompe Disease

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

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 Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

University of California-Irvine
Irvine, California 92697
Contact:
Study Coordinator
714-790-8554
kbjazevi@hs.uci.edu

Duke University School of Medicine - Early Phase Research Unit
Durham, North Carolina 27710
Contact:
Study Coordinator
919-414-6998
Janet.blount@duke.edu

The Lysosomal & Rare Disorders Research & Treatment Center
Fairfax, Virginia 22030
Contact:
Study Coordinator
571-732-4575
aagha@ldrtc.org

More Details

Status
Recruiting
Sponsor
Denali Therapeutics Inc.

Study Contact