Overview
Sponsor-declared trial summary
Glycogen storage disease type II or acid maltase deficiency, Pompe disease
To explore safety, tolerability and efficacy of avalglucosidase alfa in patients with nonclassic Pompe disease aged ≥ 5 years of whom clinical condition deteriorates while on standard treatment with alglucosidase alfa.
Key facts
- Sponsor
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Trial duration
- 16 Oct 2024 → ongoing
- Decision date (initial)
- 2024-10-16
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-518215-18-00
- EudraCT number
- 2019-002251-42
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy, Therapy, Pharmacokinetic
To explore safety, tolerability and efficacy of avalglucosidase alfa in patients with nonclassic Pompe disease aged ≥ 5 years of whom clinical condition deteriorates while on standard treatment with alglucosidase alfa.
Conditions and MedDRA coding
Glycogen storage disease type II or acid maltase deficiency, Pompe disease
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 24.0 | LLT | 10036143 | Pompe´s disease | 10010331 |
| 24.0 | LLT | 10075701 | Pompe´s disease juvenile onset | 10010331 |
| 24.0 | LLT | 10075703 | Pompe´s disease adult onset | 10010331 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- Age ≥ 5 years and ≤ 55 years.
- Childhood or juvenile/young adult onset.
- Residing in the Netherlands
- Current enzyme-replacement therapy with alglucosidase alfa ≥ 2 years (dose regimen 20 or 40 mg/kg bi-weekly).
- Confirmed diagnosis: enzyme deficiency in any tissue source and/or 2 confirmed disease-causing variants in the GAA gene.
- Willing and able to adhere to study procedures (incl. patient and/or parent/guardian signed informed consent).
- Deterioration in pulmonary function and/or 6MWT and/or muscle strength despite current treatment regimen with alglucosidase alfa.
- Disease status: Measurable pulmonary (dys)function: (F)VC ≤ 80% predicted (mechanic ventilation during the day or night allowed). Measurable muscle weakness in proximal and/or distal muscle groups (non- ambulant/wheelchair bound patients allowed). Measurable functional ability.
Exclusion criteria 6
- Age >55 years.
- Invasive mechanical ventilation.
- No remaining useful functional ability (e.g. (almost) tetraplegic), as decided by the treating physician.
- Unmanageable, severe IARs on alglucosidase alfa.
- Deterioration due to high levels of anti-alglucosidase alfa antibodies interfering with treatment efficacy.
- Female patient of childbearing potential not protected by highly effective contraceptive method of birth control and/or who is unwilling or unable to be tested for pregnancy
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 3
- Safety and tolerability are determined by assessing: • The number of AE’s/treatment-emergent adverse events, including infustion associated reactions • The occurrence of antibodies against avalglucosidase alfa • Clinical laboratory evaluations aimed at liver and muscle function (ASAT/ALAT/CK)
- Pharmacokinetics: • Single and multiple dose estimates for Cmax, AUC, CL
- Efficacy is determined by assessing: • Changes in muscle strength: Manual Muscle Testing (MMT), Hand-Held dynamometry (HHD) • Changes in muscle function: Quick Motor Function Test (QMFT), 6-Minute Walk Test(6-MWT), Timed tests • Changes in the pulmonary function o Forced vital capacity in sitting and supine positions, Maximum Inpiratory Pressure (MIP), Maximum Expiratory Pressure (MEP) • Changes in PRO-Measures: Rasch-build Pompe Activity Scale (R-PaCT), Quality of life, modified Borg scale
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Nexviadyme 100 mg powder for concentrate for solution for infusion
PRD9787959 · Product
- Active substance
- Avalglucosidase Alfa
- Substance synonyms
- NEOGAA, RECOMBINANT HUMAN ALFA-GLUCOSIDASE CONJUGATED WITH SYNTHETIC BISMANNOSE-6-PHOSPHATE-MAN6 GLYCAN, GZ402666, RECOMBINANT HUMAN ALPHA-GLUCOSIDASE CONJUGATED WITH MULTIPLE COPIES OF SYNTHETIC BISMANNOSE-6-PHOSPHATE-TETRA-MANNOSE GLYCAN
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENIOUS INFUSION
- Max daily dose
- 20 mg/kg milligram(s)/kilogram
- Max total dose
- 20 mg/kg milligram(s)/kilogram
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- A16AB22 — -
- Marketing authorisation
- EU/1/21/1579/001
- MA holder
- SANOFI B.V.
- MA country
- Liechtenstein
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Sponsor organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Address
- Dr. Molewaterplein 40
- City
- Rotterdam
- Postcode
- 3015 GD
- Country
- Netherlands
Scientific contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- Lianne Potters
Public contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- Lianne Potters
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ongoing, recruiting | 6 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2024-10-16 | 2024-10-16 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 7 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol EU CT 2024-518215-18-00 | 6 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_blank document | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 12-16 yr | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 5-12 yr | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults | 4 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF parents | 4 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Nexviadyme | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-09-24 | Netherlands | Acceptable with conditions 2024-10-16
|
2024-10-16 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-02-05 | Netherlands | Acceptable with conditions 2024-10-16
|
2025-02-05 |