32 Participants NeededMy employer runs this trial

DNL952 for Pompe Disease

CT
Overseen ByClinical Trials at Denali Therapeutics
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Denali Therapeutics Inc.
Must be taking: Avalglucosidase alfa, Cipaglucosidase alfa
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, DNL952, for individuals with late-onset Pompe disease, a condition affecting muscle function. The main goal is to determine the treatment's safety and tolerance at different doses. Participants will be grouped into cohorts to test various aspects of the treatment. Ideal candidates can walk at least 40 meters, have a diagnosis of late-onset Pompe disease, and possess specific prior treatment experience. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, if you are in Cohorts A1-A4, you must have been on specific enzyme-replacement therapies for at least 12 months before screening. If you are in Cohorts B1-B2, you must not have received any enzyme-replacement therapy for Pompe disease in the 12 months before screening.

Is there any evidence suggesting that DNL952 is likely to be safe for humans?

Earlier research on DNL952 revealed some safety concerns. In animal studies, mice experienced strong allergic reactions, which are intense immune responses. Due to these reactions, the FDA temporarily halted plans to test DNL952 in humans. However, this pause was later lifted, allowing the current trial to proceed.

This treatment remains in the early stages of human testing. The primary goal is to assess its safety and tolerability. As DNL952 undergoes its first human trials, detailed safety information for humans is not yet available. Participants in the trial will contribute valuable data on the treatment's safety and tolerability.12345

Why do researchers think this study treatment might be promising for Pompe disease?

Unlike the standard treatments for Pompe disease, which typically involve enzyme replacement therapies (ERTs) like alglucosidase alfa, DNL952 offers a unique approach. Researchers are excited because DNL952 is designed to cross the blood-brain barrier more effectively, potentially addressing neurological symptoms that current treatments cannot. This new mechanism of action could provide a more comprehensive treatment option for patients with late-onset Pompe disease (LOPD), expanding beyond the capabilities of existing therapies.

What evidence suggests that DNL952 might be an effective treatment for Pompe disease?

Research has shown that DNL952 is a new type of treatment called enzyme replacement therapy (ERT). It aims to enhance enzyme function in muscles and the nervous system for individuals with Pompe disease. While current ERTs have been beneficial, they still face challenges, particularly in muscles and the brain. Early studies in mice revealed some immune reactions, which are now being carefully studied in humans. The treatment seeks to improve enzyme delivery, potentially aiding muscle and breathing issues in late-onset Pompe disease. Although human studies have provided limited information, the approach appears promising based on its mechanism. Participants in this trial will join various cohorts to assess the effectiveness and safety of DNL952.12567

Who Is on the Research Team?

MM

Medical Monitor

Principal Investigator

Denali Therapeutics Inc.

Are You a Good Fit for This Trial?

This trial is for adults diagnosed with late-onset Pompe disease who can walk at least 40 meters (with or without help) and have reasonably good lung function. Some groups must not have had enzyme-replacement therapy in the past year, while others must have been on specific treatments for at least a year.

Inclusion Criteria

I meet the main requirements for this study.
My body weight is at least 40 kilograms.
I have been diagnosed with late-onset Pompe disease.
See 4 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DNL952 to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • DNL952

Trial Overview

The study is testing different doses of a new drug called DNL952 to see how safe it is and how the body processes it in adults with late-onset Pompe disease. All participants will receive DNL952, and researchers will monitor their responses closely.

How Is the Trial Designed?

6

Treatment groups

Experimental Treatment

Group I: Cohort B2 (Optional)Experimental Treatment1 Intervention
Group II: Cohort B1 (Optional)Experimental Treatment1 Intervention
Group III: Cohort A4 (Optional)Experimental Treatment1 Intervention
Group IV: Cohort A3 (Optional)Experimental Treatment1 Intervention
Group V: Cohort A2Experimental Treatment1 Intervention
Group VI: Cohort A1Experimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Denali Therapeutics Inc.

Lead Sponsor

Trials
24
Recruited
1,900+

Citations

A Phase 1, Multicenter, Open-Label Study Design to ...

DNL952 is a novel, investigational ERT for Pompe disease that has been designed to enhance GAA delivery to muscles and to the nervous system.

NCT07354724 | A Study to Evaluate the Safety, ...

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

Screening data from 19 patients with late‐onset Pompe ... - PMC

We present clinical parameters and AAV antibody titers for 19 individuals with LOPD undergoing screening for a Phase I clinical trial with an AAV serotype 8 ...

FDA Clinical Hold on Denali's Brain-Penetrant Pompe ...

Existing ERTs have improved outcomes but leave significant residual burden, particularly in skeletal muscle and the central nervous system. If ...

Denali ph. 1 Pompe plans hit with clinical hold

The issue stems from overactive immune responses, called hypersensitivity reactions, in mice given DNL952, a therapy meant to restore acid alpha ...

FDA Pauses Denali's Pompe Plans Due to Preclinical ...

Hypersensitivity reactions in a mouse model prompted the agency to suspend Denali's planned Phase I development for DNL952 for Pompe disease.

Release Details

The study is intended to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of DNL952. Preclinical data also presented at ...