A phase 2, randomized, double-blind study of S-606001 as an add-on to enzyme replacement therapy in patients with late-onset Pompe disease.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Shionogi B.V.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

12 Feb 2026 → ongoing

Decision date (initial)

2025-12-03

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Shionogi

External identifiers

EU CT number

2025-522146-40-00

WHO UTN

U1111-1323-0409

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Safety, Pharmacokinetic

To evaluate the preliminary effect of S-606001 as an add-on to enzyme replacement therapy (ERT) on lung function in participants with late-onset Pompe disease (LOPD).

Secondary objectives 5

1. 1. To evaluate the safety and tolerability profile of S-606001 as an add-on to enzyme replacement therapy (ERT) in participants with late-onset Pompe disease (LOPD).
2. 2. To evaluate the pharmacokinetics of S-606001 as an add-on to ERT in participants with LOPD.
3. 3. To evaluate the pharmacodynamics of S-606001 as an add-on to ERT in participants with LOPD.
4. 4. To evaluate the effect of S-606001 as an add-on to ERT on motor function in participants with LOPD.
5. 5. To assess the exploratory clinical effects including physical functions and patient-reported outcomes of S-606001 as an add on to ERT in participants with LOPD.

Conditions and MedDRA coding

Late-onset Pompe disease.

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, Medicines Evaluation Board, Federal Institute For Drugs And Medical Devices

Plan to share IPD

Yes

IPD plan description

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://www.shionogi.com/global/en/company/policies/shionogi-group-clinical-trial-data-transparency-policy.html In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Shionogi B.V will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://www.shionogi.com/global/en/innovation/randd/clinical-development/clinical-trial-data/clinical-trial03.html

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Participant must be ≥ 18 years and ≤ 65 years of age and ≥ 40 kg of body weight at the time of signing the informed consent.
2. 2. Participant must have a diagnosis of LOPD based on documentation of 1 of the following: a. Deficiency of acid alpha-glucosidase (GAA) enzyme b. GAA genotype; previous results of GAA genotyping will be acceptable for eligibility assessment.
3. 3. Participant has a %Forced Vital Capacity (FVC) ≥ 30% and ≤ 80% in an upright position without mechanical ventilation at screening; or Participant has ≥ 10% %FVC drop from upright position to supine position and %FVC ≥ 20% in a supine position.
4. 4. Participant performs the 6-minute walk test (6MWT) at screening, as determined by the clinical evaluator, and meets all of the following criteria: a. Screening values of 6-minute walk distance (6MWD) are ≥ 75 meters b. Screening values of 6MWD are ≤ 90% of the predicted value for healthy adults.
5. 5. a. Male participants: Male participants are eligible to participate if they agree to the following during the intervention period and for at least 14 weeks after the last dose of investigational intervention: Refrain from donating fresh unwashed semen PLUS either: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR Must agree to use contraception/barrier as detailed in the protocol. b. Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies: Is not a woman of childbearing potential (WOCBP) as defined in the protocol OR is a WOCBP and using a contraceptive method that is highly effective preferably with low user dependency, as described in the protocol during the intervention period and for at least 184 days after the last dose of investigational intervention, and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of investigational intervention.
6. 6. Capable of giving signed informed consent prior to any study-related procedures being performed that includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
7. 7. Participants must be ERT-experienced.

Exclusion criteria 22

1. 1. Has a medical condition or any other extenuating circumstance that may, in the opinion of the investigator or medical monitor, pose an undue safety risk to the participant or may compromise his/her ability to comply with or adversely impact protocol requirements.
2. 2. Requires the use of invasive or noninvasive ventilation support while awake.
3. 3. Has active infections at screening, including but not limited to viral hepatitis, HIV infection, or pulmonary tuberculosis. If the infection is acute and resolved before day 1, the participant may be enrolled.
4. 4. Malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
5. 5. Total bilirubin > 1.5 × upper limit of normal (ULN; participants with Gilbert’s syndrome can be included with total bilirubin > 1.5 × ULN if direct bilirubin is ≤ 1.5 × ULN).
6. 6. Current or chronic history of liver disease, including, but not limited to: hepatitis virus infections; drug- or alcohol-related liver disease; non-alcoholic steatohepatitis; autoimmune hepatitis; hemochromatosis; Wilson’s disease; α-1 antitrypsin deficiency; primary biliary cholangitis; primary sclerosing cholangitis; or any other liver disease considered clinically significant by the investigator (eg, higher abnormal alanine aminotransferase [ALT] value with relatively lower aspartate aminotransferase [AST] value, or abnormal gamma-glutamyl transaminase value).
7. 7. Known biallelic loss of function mutations whether in GYG gene or in PYGM gene.
8. 8. QT interval corrected for heart rate according to Fridericia’s formula (QTcF) > 450 msec for male participants, QTcF > 470 msec for female participants, or QTcF > 480 msec in participants with bundle branch block. NOTE: The QTcF is either machine-read or manually over-read.
9. 9. Has poorly controlled glycemia (ie, HbA1c > 7%).
10. 10. Has bleeding disorders or clinically significant abnormal values in prothrombin or activated partial thromboplastin time (in the investigator's opinion).
11. 11. Has chronic obstructive pulmonary disease or any other chronic pulmonary disorders including active or latent lung tuberculosis.
12. 12. Has any known significant cardiac malfunction, including a history of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) and the use of concomitant medications that prolong the QT/QTc interval.
13. 13. Has received any investigational therapy or pharmacological treatment for Pompe disease, within 30 days or 5 half-lives of the therapy or treatment, whichever is longer, before day 1 or is anticipated to do so during the study.
14. 14. Has received gene therapy or small interfering RNA therapy for Pompe disease.
15. 15. Is taking any of the prohibited medications listed in the study protocol.
16. 16. Is currently enrolled in any other clinical study involving an investigational study or any other type of medical research.
17. 17. Is currently enrolled or past participation in another investigational study in which an investigational intervention (eg, drug, vaccine, invasive device) was administered within 30 days before the planned first dose of investigational intervention in this clinical study.
18. 18. Positive HIV antibody test.
19. 19. Presence of hepatitis B surface antigen or hepatitis B virus core antibody at screening or within 3 months prior to the first dose of investigational intervention.
20. 20. Positive hepatitis C virus antibody test result at screening or within 3 months prior to the first dose of investigational intervention. NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative hepatitis C virus RNA test is obtained.
21. 21. Participant, if female, is pregnant or breastfeeding at screening.
22. 22. Participant, whether male or female, is planning to conceive a child during the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in %FVC at 52 weeks.

Secondary endpoints 5

1. 1. Assessment of adverse events and treatment-emergent adverse events. Physical examinations and vital sign measurements. Clinical laboratory evaluations including biochemistry, hematology, and urinalysis. Electrocardiograms.
2. 2. Plasma concentration of S-606001.
3. 3. Change from baseline in the parameters stated in the protocol.
4. 4. Change from baseline in 6-minute walk test.
5. 5. Change from baseline in pulmonary function parameters: maximal inspiratory pressure, maximal expiratory pressure. Change from baseline in motor function parameters: Gait, Stair, Gower’s Maneuver, Chair (GSGC) score, Daily Living Activity Levels. Change from baseline in the following parameters: PROMIS-Fatigue-8a, PROMIS-PF20, PROMIS-Dyspnea, PROMIS v2.0 PAIN, SF-36, PGI-S.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Shionogi B.V.

Sponsor organisation

Shionogi B.V.

Address

Herengracht 464

City

Amsterdam

Postcode

1017 CA

Country

Netherlands

Scientific contact point

Organisation

Shionogi B.V.

Contact name

Shionogi B.V. Medical Sciences

Public contact point

Organisation

Shionogi B.V.

Contact name

Shionogi B.V. Medical Sciences

Third parties 14

Locations

7 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 69 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications