Authorised Phase I and Phase II (Integrated)- First administration to humans Late-Onset Pompe Disease

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

EU CTIS ID: 2025-524082-25-00

What this study is testing

To characterize the safety and tolerability of DNL952 in participants with LOPD

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

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

Are aged 18 to 75 years, inclusive, at screening
Are able to ambulate ≥ 40 meters on the 6MWT at screening. Use of assistive ambulatory devices (eg, cane or walker) is acceptable.
For Cohorts A1, A2, and, if opened, A3, and A4 (all enrolling ERT-experienced participants with LOPD): Must currently be receiving avalglucosidase alfa or cipaglucosidase alfa at a dose of 20 mg/kg Q2W and must have been treated for at least 12 months prior to screening with no gaps between doses of longer than 8 weeks and no missed doses in the 8 weeks prior to screening or during screening.
For Cohorts B1 and B2, if opened (all enrolling ERT-naïve participants with LOPD): Must not have received any ERT for Pompe disease in the 12 months prior to screening and have received no more than four total doses of ERT for Pompe disease at any time.
Have a body weight ≥ 40 kg
Are willing and able to give informed consent for study participation

You likely can't join if

Have any ongoing, clinically significant, unstable, or poorly controlled neurological, psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematological, immunological, allergic not related to Pompe disease, or other major disorders. Well-controlled conditions are permitted if investigator and Sponsor agree.
Are wheelchair-dependent
Have a history or presence of a clinically significant ECG abnormality, including, but not limited to, complete left bundle branch block, type 2 second- or third-degree heart block, or other abnormalities that, in the investigator’s opinion, put the participant at risk and/or preclude accurate interpretation of cardiac intervals (eg, PR, QT, QRS)
ECG abnormalities due to right bundle branch block in the absence of other significant cardiac disease or due to pacemaker may be acceptable pending investigator and Sponsor medical monitor agreement.
Have 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 and thereafter
Have donated or lost more than 500 mL whole blood within 30 days before screening

See the full eligibility criteria

Who can join

Are aged 18 to 75 years, inclusive, at screening
Are able to ambulate ≥ 40 meters on the 6MWT at screening. Use of assistive ambulatory devices (eg, cane or walker) is acceptable.
For Cohorts A1, A2, and, if opened, A3, and A4 (all enrolling ERT-experienced participants with LOPD): Must currently be receiving avalglucosidase alfa or cipaglucosidase alfa at a dose of 20 mg/kg Q2W and must have been treated for at least 12 months prior to screening with no gaps between doses of longer than 8 weeks and no missed doses in the 8 weeks prior to screening or during screening.
For Cohorts B1 and B2, if opened (all enrolling ERT-naïve participants with LOPD): Must not have received any ERT for Pompe disease in the 12 months prior to screening and have received no more than four total doses of ERT for Pompe disease at any time.
Have a body weight ≥ 40 kg
Are willing and able to give informed consent for study participation
Are able to communicate with the investigator and staff
Are willing and able to comply with the requirements of the study, including scheduled visits, study restrictions, laboratory tests, and all other study procedures
6a. Female participants of childbearing potential are permitted in the study and, if sexually active with a male partner, must use an acceptable highly effective method of contraception (Table 12) from at least 30 days prior to the core study period, throughout the core and extension study periods, and for 90 days after the final administration of study intervention 6b. Female participants of non-childbearing potential are permitted in the study and include female participants who have been surgically sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy; proper documentation required) at least 3 months prior to dosing, and female participants who are postmenopausal
For male participants: When engaging in sex with a female participant of childbearing potential, the male participant and female partner must use two forms of birth control—a male barrier method such as a latex or polyurethane condom and an acceptable highly effective method (Table 12)—from the start of dosing, throughout the core and extension study periods, and for 90 days after the final administration of study intervention. 7a. Male participants must not donate sperm at any time from the start of dosing, throughout the clinical study period, and for 90 days after the final administration of study intervention.
Have a diagnosis of LOPD, defined as meeting both of the following criteria: a. Two pathogenic or likely pathogenic variants (excluding pseudodeficiency alleles) in the GAA gene (based on historical records available for review by investigator or Sponsor, or genetic testing at screening) b. No known history of clinically significant Pompe-related cardiac hypertrophy in the first year of life
Have an upright FVC ≥ 30% of predicted normal value at screening. Patients may be rescreened if their clinical condition changes. Patients who failed screening because their FVC % predicted was below the cutoffs above due to intercurrent illness may rescreen after the illness resolves.

What rules you out

Have any ongoing, clinically significant, unstable, or poorly controlled neurological, psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematological, immunological, allergic not related to Pompe disease, or other major disorders. Well-controlled conditions are permitted if investigator and Sponsor agree.
Are wheelchair-dependent
Have a history or presence of a clinically significant ECG abnormality, including, but not limited to, complete left bundle branch block, type 2 second- or third-degree heart block, or other abnormalities that, in the investigator’s opinion, put the participant at risk and/or preclude accurate interpretation of cardiac intervals (eg, PR, QT, QRS)
ECG abnormalities due to right bundle branch block in the absence of other significant cardiac disease or due to pacemaker may be acceptable pending investigator and Sponsor medical monitor agreement.
Have 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 and thereafter
Have donated or lost more than 500 mL whole blood within 30 days before screening
Have been hospitalization due to acute illness during the 4 weeks prior to screening. Brief stays for monitoring or minor elective procedures may be permitted with agreement of the investigator and Sponsor.
Are an employee of the Sponsor or research site personnel directly affiliated with this study or their immediate family members, defined as a spouse, parent, child, or sibling, whether biological or legally adopted
Have any other issue that, in the opinion of the investigator, would make the participant ineligible for study participation due to a potential risk to the participant’s safety or ability to comply with study procedures.
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.
Have a positive serum pregnancy test or currently lactating or breastfeeding
Have had suicidal ideation, as assessed by the C-SSRS at screening, in the prior 6 months (a “yes” response to questions 1 and/or 2 on the Suicidal Ideation section with Intensity of Ideation scores ≤ 2 may be allowed pending investigator and Sponsor medical monitor agreement) or a lifetime suicide attempt (as defined by a “yes” response to lifetime actual, interrupted, or aborted attempt on the Suicidal Behavior section; a lifetime suicide attempt > 5 years before screening may be allowed pending investigator and Sponsor medical monitor agreement)
Are currently receiving systemic treatment(s) for malignancy, or have a history of malignancy within 5 years before screening, except fully resected basal cell carcinoma or other treated malignancies at low risk of recurrence, depending on investigator and medical monitor agreement.
Have a history of severe hypersensitivity reaction or anaphylaxis to any ERT for Pompe disease, or history of severe allergy or hypersensitivity to any of the excipients contained within the DNL952 study drug product
Have used any of the following prohibited medications within 7 days of screening or intend to use any during the study: miglitol, acarbose, and voglibose
Have a history of alcohol or substance use disorder, as defined by the DSM-5 criteria for moderate to severe substance use disorder, in the 12 months prior to screening
Have used any smoked or inhaled tobacco, marijuana, or related products, including vaping, within 3 months before screening
Have a positive drug screen (not including cannabinoids) with positive confirmatory drug test at screening
Have renal impairment, as indicated by an estimated glomerular filtration rate < 90 mL/min/1.73 m2 at screening, ( as estimated with the CKD-EPI cystatin C equation) or urine albumin-to-creatinine ratio > 300 mg/g, or history of immune complex–mediated nephropathy
Have other clinical laboratory test values outside of the normal range at screening, unless assessed by the investigator as clinically nonsignificant values. Clinically significant elevations in creatine kinase related to Pompe disease, in the opinion of the investigator, are permitted.
Have positive serology for HIV, HBV (positive anti-HBc with negative hepatitis B DNA is acceptable), or HCV (treated/resolved HCV infection with negative PCR RNA is allowed)
Have a supine SBP < 90 or > 160 mmHg, pulse rate < 40 or > 110 bpm, or elevated body temperature (≥ 100.4°F [38°C]) at screening Note: Blood pressure, heart rate, and temperature measurements may be repeated up to three times during the screening period if initial measurements are considered to be atypical for the participant.

The study team makes the final eligibility decision.

Where it's taking place

United States
United Kingdom

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include United States; United Kingdom. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.