A Study to Evaluate the Safety, Efficacy, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of cipaglucosidase alfa/miglustat in both ERT-experienced and ERT-naïve children under 18 Years with Infantile-onset Pompe Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amicus Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

4 Nov 2024 → ongoing

Decision date (initial)

2026-03-30

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2022-501095-25-01

ClinicalTrials.gov

NCT04808505

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Pharmacokinetic, Efficacy, Pharmacodynamic

To evaluate the safety and tolerability of co-administration of cipaglucosidase alfa/miglustat in enzyme replacement therapy (ERT)-experienced subjects with infantile-onset Pompe disease (IOPD) aged 6 months to < 18 years and in ERT-naïve subjects with IOPD aged 0 to < 6 months

Secondary objectives 1

1. To evaluate the efficacy of co-administration of cipaglucosidase alfa/miglustat in ERT-experienced subjects with IOPD aged 6 months to < 18 years and in ERT-naïve subjects with IOPD aged 0 to < 6 months

Conditions and MedDRA coding

Pediatric Subjects with Infantile-onset Pompe Disease Aged 0 to < 18 Years

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002447-PIP01-18

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Cohort 1: 1. Male or female subjects who are aged 6 months to < 18 years on Day 1.
2. Cohort 1: 2. Subject's parent or legally authorized representative is willing and able to provide written informed consent and authorization for study participation and use and disclosure of personal health information or research-related health information.
3. Cohort 1: 3. Subject must have documentation of bi-allelic gene encoding human acid α-glucosidase (GAA) variants prior to initiation of study drug.
4. Cohort 1: 4. Subject must have had hypertrophic cardiomyopathy at the time of diagnosis defined as: • > 1 standard deviation above the mean age-specific left ventricle mass index (LVMI) for subjects diagnosed by newborn screening or sibling screening • > 2 standard deviations above the mean age-specific LVMI for subjects diagnosed by clinical evaluation
5. Cohort 1: 5. Subject must have received ERT for at least 6 months immediately before enrollment. For subjects whose ERT dosage has been modified, the subject must have been on the modified dosage and regimen for at least 3 months before enrollment.
6. Cohort 1: 6. Subject must have experienced a clinical decline based on the protocol-specified criteria on their current rhGAA dose and frequency.
7. Cohort 1: 7. If of reproductive potential and sexually active, female and male subjects must agree to use a highly effective method of contraception throughout the duration of the study and for at least 90 days after their last dose of cipaglucosidase alfa/miglustat.
8. Cohort 1: 8. For subjects aged ≥ 12 to < 18 years, subject must perform one 6-minute walk test (6MWT) (≥ 75 meters) at screening that is valid, as determined by the clinical evaluator; for subjects aged ≥ 5 to < 12 years, subject must perform one 6MWT (≥ 40 meters) at screening that is valid, as determined by the clinical evaluator. Subjects aged 18 months to < 5 years must be ambulatory and in the opinion of the investigator assessed to be likely to be able to perform 6MWT (≥ 40 meters) when they turn 5 years old.
9. Cohort 2: 1. Male or female subjects who are aged 0 to < 6 months at on Day 1.
10. Cohort 2: 2. Subject’s parent or legally authorized representative is willing and able to provide written informed consent and authorization for study participation and use and disclosure of personal health information or research-related health information.
11. Cohort 2: 3. Subject must have documentation of bi-allelic gene encoding human acid α-glucosidase (GAA) variants prior to initiation of study drug.
12. Cohort 2: 4. Subject must have had hypertrophic cardiomyopathy at the time of diagnosis defined as: • > 1 standard deviation above the mean age-specific LVMI for subjects diagnosed by newborn screening or sibling screening • > 2 standard deviations above the mean age-specific LVMI for subjects diagnosed by clinical evaluation
13. Cohort 2: 5. Subject is ERT-naïve (having had no prior ERT-treatment).
14. Long-term Extension (Cohort 1 or Cohort 2) Inclusion Criteria: 1. Subject must have, in the opinion of the investigator, benefitted from therapy with cipaglucosidase alfa/miglustat during the 104-week primary treatment period (Stage 1) with no significant safety concerns.

Exclusion criteria 19

1. Cohort 1: 1. Subject requires invasive ventilation (eg, tracheostomy).
2. Cohort 1: 2. Subject requires respiratory assistance for ≥ 16 hours per day (including noninvasive ventilator support) continuously for ≥ 14 days in the absence of an acute reversible illness, excluding perioperative ventilation.
3. Cohort 1: 3. Subject received any investigational drug or any investigational biologic for Pompe disease within 30 days or 5 half-lives of the therapy or treatment, whichever is longer, before screening.
4. Cohort 1: 4. Subject is CRIM-negative and has not received prophylactic immunomodulation.
5. cohort 1: 5. Subject has received any gene therapy within the past 3 years.
6. Cohort 1: 6. Subject has any intercurrent illness or condition at screening or baseline that may preclude the subject from fulfilling the protocol requirements or suggests to the investigator and/or the medical monitor that the potential subject may have an unacceptable risk by participating in this study.
7. Cohort 1: 7. Subject has any prior history of illness or condition known to affect motor function, such as, but not limited to, Guillain Barre syndrome, cerebral palsy, etc.
8. Cohort 1: 8. Subject has a history of life-threatening infusion-associated reactions (IARs)/hypersensitivity (eg, anaphylaxis and severe cutaneous reactions) to ERT (eg, alglucosidase alfa, cipaglucosidase alfa), miglustat, or other iminosugars, or to any of the excipients, where rechallenge was unsuccessful.
9. Cohort 1: 9. Female subject is pregnant (or intends to get pregnant) or breastfeeding at screening.
10. Cohort 1: 10. In the opinion of the investigator, the parent or legally authorized representative is unlikely or unable to comply with the study requirements.
11. Cohort 2: 1. Subject requires invasive ventilation (eg, tracheostomy).
12. Cohort 2: 2. Subject requires respiratory assistance for ≥ 16 hours per day (including noninvasive ventilator support) continuously for ≥ 14 days in the absence of an acute reversible illness, excluding perioperative ventilation.
13. Cohort 2: 3. Subject received any investigational drug or any investigational biologic for Pompe disease within 30 days or 5 half-lives of the therapy or treatment, whichever is longer, before screening.
14. Cohort 2: 4. Subject is CRIM-negative and will not be receiving prophylactic immunomodulation.
15. Cohort 2: 5. Subject has received any gene therapy at any time.
16. Cohort 2: 6. Subject has any intercurrent illness or condition at screening or baseline that may preclude the subject from fulfilling the protocol requirements or suggests to the investigator and/or the medical monitor that the potential subject may have an unacceptable risk by participating in this study.
17. Cohort 2: 7. Subject has any prior history of illness or condition known to affect motor function, such as, but not limited to, Guillain Barre syndrome, cerebral palsy, etc.
18. Cohort 2: 8. Subject has a history of life-threatening IARs/hypersensitivity (eg, anaphylaxis and severe cutaneous reactions) to ERT (eg, alglucosidase alfa, cipaglucosidase alfa), miglustat, or other iminosugars, or to any of the excipients, where rechallenge was unsuccessful.
19. Cohort 2: 9. In the opinion of the investigator, the parent or legally authorized representative is unlikely or unable to comply with the study requirements.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the proportion of subjects with infusion-associated reactions (IARs).

Secondary endpoints 5

1. incidence of treatment-emergent adverse events (TEAEs), including treatment-emergent serious adverse events (TESAEs), hypersensitivity/anaphylactic reactions, and TEAEs leading to discontinuation of study drug
2. changes in clinical laboratory test results
3. changes in vital signs
4. changes in 12-lead ECG results
5. changes in echocardiogram parameters (other than LVMI)

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amicus Therapeutics Inc.

Sponsor organisation

Amicus Therapeutics Inc.

Address

47 Hulfish Street

City

Princeton

Postcode

08542-3713

Country

United States

Scientific contact point

Organisation

Amicus Therapeutics Inc.

Contact name

Amicus Patient Advocacy

Public contact point

Organisation

Amicus Therapeutics Inc.

Contact name

Amicus Patient Advocacy

Third parties 8

Locations

5 EU/EEA countries · 10 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 66 files

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

Application history

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