Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of DNL952 in Adults with Late‑Onset Pompe Disease

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What is this study about?

Late-Onset Pompe Disease is a rare inherited condition that causes muscles to become weak because a type of sugar builds up inside them. The study will use a medication called DNL952, which is given by intravenous infusion – a slow drip of medicine through a vein.

The purpose of the study is to assess the safety and tolerability of DNL952 in adults with Late-Onset Pompe Disease. Participants will receive the infusion at several clinic visits and will be checked for any side effects. Small blood samples will be taken to understand the drug’s pharmacokinetics (how the body absorbs, moves, and clears the medicine) and pharmacodynamics (how the medicine works in the body). The study will also look for the development of ADAs, which are antibodies the body might produce against the drug. The overall time in the study is a few months, with regular monitoring to ensure participant safety.

1 baseline assessments

after joining the study, the patient attends a baseline visit.

during this visit, medical history, a physical examination, and laboratory tests are performed to confirm the diagnosis of late-onset pompe disease and to record the patient’s health status before receiving any study medication.

2 first infusion of dnl952

the patient receives the first dose of dnl952 as an intravenous infusion (medicine delivered through a vein using a drip).

the exact amount of medicine and the speed of the infusion are set by the study protocol; these details are not disclosed in this summary.

the infusion may take several minutes to a few hours, depending on the protocol.

3 post‑infusion observation

after the infusion, the patient remains in the clinic for a monitoring period.

health care staff watch for any infusion‑related reactions, such as fever, rash, or breathing changes, and record any symptoms.

4 scheduled follow‑up visits

the patient returns for regular follow‑up visits according to the study schedule (for example, weekly or monthly).

each visit includes safety checks, a physical exam, and laboratory tests.

blood samples are taken to measure dnl952 levels in the blood (pharmacokinetics) and to check for antibodies that the body might produce against the medicine.

5 additional infusions (if required)

if the study protocol calls for more than one dose, the patient receives additional dnl952 infusions at the specified intervals (for example, every four weeks).

each infusion follows the same procedure as the first infusion, including the post‑infusion observation period.

6 ongoing safety and tolerability assessments

throughout the trial, the patient continues to undergo safety evaluations, which may include symptom questionnaires, physical examinations, and laboratory tests.

the purpose is to record any adverse events and to determine how well the patient tolerates the study medication.

7 final study visit

at the end of the study period, the patient attends a final visit.

the final visit includes a comprehensive health assessment, collection of final blood samples, and documentation of any remaining study medication effects.

after this visit, the patient stops receiving the study medication.

Who Can Join the Study?

Age must be between 18 and 75 years at the time of screening.
You must be able to walk at least 40 meters in a six‑minute walk test (6MWT); using a cane or walker is allowed.
If you are already receiving enzyme replacement therapy (ERT) with avalglucosidase alfa or cipaglucosidase alfa at a dose of 20 mg per kilogram every two weeks, you must have been on this treatment for at least 12 months with no gaps longer than 8 weeks and no missed doses in the 8 weeks before screening.
If you have not received ERT (or have had no more than four doses total), you must not have had any ERT in the 12 months before screening.
Body weight must be at least 40 kg (about 88 lb).
You must be willing and able to give written informed consent to join the study.
You must be able to communicate with the study doctor and staff.
You must be willing and able to follow all study requirements, such as scheduled visits, laboratory tests, and other procedures.
Female participants who could become pregnant must use a highly effective birth‑control method (as listed in the study) starting at least 30 days before the first dose and continuing through the study and for 90 days after the last dose.
Female participants who cannot become pregnant (because they have had a hysterectomy, removal of both ovaries, removal of both fallopian tubes, or are post‑menopausal) are also allowed.
Male participants who have sex with a female who could become pregnant must use two forms of birth control: a condom plus a highly effective method, from the start of dosing through the study and for 90 days after the last dose.
Male participants must not donate sperm from the start of dosing through the study and for 90 days after the last dose.
You must have a confirmed diagnosis of late‑onset Pompe disease, which means having two disease‑causing changes in the GAA gene (excluding harmless variants) and no significant heart enlargement (cardiac hypertrophy) during the first year of life.
Your upright forced vital capacity (FVC) must be at least 30 % of the predicted normal value at screening; if a temporary illness lowers this number, you may be screened again after recovery.

Who Cannot Join the Study?

Having ongoing, serious, unstable, or poorly controlled neurological (brain and nerve), psychiatric (mental health), endocrine (hormone), lung (breathing), heart (cardiovascular), stomach/intestine (gastro‑intestinal), liver (hepatic), pancreas, kidney (renal), metabolism, blood (hematology), immune (immunology), or allergy problems that are not related to Pompe disease; well‑controlled conditions may be allowed if the doctor agrees.
Being dependent on a wheelchair for movement.
Having a serious abnormal heart test called an ECG (electrocardiogram) such as a complete left bundle branch block, type 2 second‑ or third‑degree heart block, or other irregularities that could put you at risk or make heart‑interval measurements inaccurate.
Having an ECG abnormality caused only by a right bundle branch block without other heart disease or having a pacemaker may be allowed if the doctor approves.
Having received experimental gene therapy, taken part in another drug study, or used an investigational drug within 60 days (or five drug half‑lives, whichever is longer) before screening.
Donating or losing more than 500 mL of whole blood (about one pint) within 30 days before screening.
Being hospitalized for an acute (sudden) illness in the 4 weeks before screening (short stays for monitoring or minor procedures may be allowed with doctor approval).
Being an employee of the study sponsor or the research site, or being an immediate family member (spouse, parent, child, or sibling) of those employees.
Any other issue that the doctor believes makes participation unsafe or would prevent you from following the study procedures.
Needing non‑invasive breathing support (such as a mask) for more than 6 hours per day while awake, or any invasive breathing support (such as a tube); using non‑invasive support only while sleeping is allowed.
Having a positive pregnancy test, being currently pregnant, or breastfeeding.
Having thoughts of suicide in the past 6 months or a lifetime suicide attempt (unless it was more than 5 years ago and the doctor agrees).
Currently receiving systemic treatment for cancer, or having had cancer within the past 5 years, except for fully removed basal cell skin cancer or other low‑risk cancers (may be allowed with doctor approval).
Having a severe allergic reaction (hypersensitivity) or anaphylaxis (a life‑threatening allergy) to any enzyme replacement therapy (ERT) for Pompe disease, or to any ingredient (excipients) in the study drug.
Using any of the following diabetes medicines within 7 days of screening or planning to use them during the study: miglitol, acarbose, or voglibose.
Having a history of moderate to severe alcohol or substance use disorder in the past 12 months, as defined by the DSM‑5 (a standard manual for diagnosing mental health conditions).
Using smoked or inhaled tobacco, marijuana, or related products (including vaping) within 3 months before screening.
Having a positive drug test (excluding cannabinoids) at the screening visit.
Having kidney problems, defined as an estimated glomerular filtration rate (eGFR) less than 90 mL/min/1.73 m² or a urine albumin‑to‑creatinine ratio greater than 300 mg/g, or a history of immune‑complex kidney disease.
Having any laboratory test results outside the normal range at screening, unless the doctor decides they are not clinically important (elevated creatine kinase due to Pompe disease may be allowed).
Testing positive for HIV, hepatitis B (HBV), or hepatitis C (HCV) infection (certain treated cases may be allowed).
Having low or high blood pressure while lying down (systolic  160 mmHg), a very slow or fast heart rate (pulse  110 beats per minute), or a fever (temperature ≥ 100.4 °F / 38 °C) at screening.

Where you can join this trial?

Verified and Recommended Sites

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Verified Sites

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Other Sites

Site Name	City	Country	Status
SphinCS GmbH	Hochheim Am Main	Germany
Engrvld Urplqptshelq Mnnuazs Chogeuq Rfntqyxpo (uxpeuhw Msx	Rotterdam	The Netherlands

Trial status

Country	Status	Recruitment Start
Germany	Not yet recruiting	30.07.2026
The Netherlands	Not yet recruiting	30.07.2026

Trial locations

DNL952 is an experimental drug being given by an intravenous (IV) infusion. In this early‑stage study, the medicine is being tested in adults who have late‑onset Pompe disease to see if it is safe and well‑tolerated. Researchers will also look at how the drug moves through the body (pharmacokinetics) and how it affects the disease (pharmacodynamics). The goal is to gather information that could help develop new treatments for this condition.

Investigated diseases:

Glycogen storage disease type II

Late-Onset Pompe disease – Late-Onset Pompe disease is a genetic condition that causes a buildup of glycogen in muscle cells. It typically appears in childhood, adolescence, or adulthood and leads to gradual muscle weakness. Over time, the weakness can spread to the legs, hips, and muscles used for breathing. People may notice difficulty walking, climbing stairs, or taking deep breaths. Symptoms often become more noticeable as the individual gets older.

Trial ID:

2025-524082-25-00

Protocol code:

DNLI-J-0001

Trial Phase:

Phase I and Phase II (Integrated) – First administration to humans

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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of DNL952 in Adults with Late‑Onset Pompe Disease

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?