Treatment frequency Reduction In POmpe disease (TRIPO-Study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

26 Jun 2025 → ongoing

Decision date (initial)

2024-11-21

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Therapy

The primary objective is to explore whether less frequent treatment with ERT (once every 4 weeks instead of once every 2 weeks) does not lead to increased progression of muscle strength, muscle function and pulmonary function in a selected group of elderly patients with LOPD who is in a stable condition (not requiring wheelchair use and respiratory support during the day while awake and seated), and who is at no immediate risk of losing the ability to carry out important activities of daily living (ADLs).
If this less frequent treatment regimen (once every 4 weeks instead of once every 2 weeks) proves to be safe for a period of 9 months, and does not lead to increased disease progression, we aim to investigate whether treatment can eventually be discontinued.

Secondary objectives 1

1. The secondary objectives are to investigate potential biomarkers (tetraglucoside and two unpublished novel candidate biomarkers) in serum and urine to predict disease activity and response to ERT, to collect pharmacokinetic (PK) blood samples for internal validation of a currently constructed population pharmacokinetic/pharmacodynamic (popPK/PD) model for alglucosidase alfa and for construction of a popPK/PD model for avalglucosidase alfa and cipaglucosidase alfa, to perform serological testing of creatine kinase (CK), and to measure antibody titers (in blood) against alglucosidase alfa, avalglucosidase alfa or cipaglucosidase alfa (as this may impair the clinical efficacy of ERT). Furthermore, we will measure changes in lean body mass with DEXA scans and monitor the use of walking devices and artificial ventilation.

Conditions and MedDRA coding

Pompe disease

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. To be eligible for this study, a subject must meet all of the following criteria: • LOPD (confirmed diagnosis: enzyme deficiency in any tissue source and/or 2 confirmed disease-causing variants in the GAA gene) • Age ≥50 years • Current treatment with ERT at a standard dose of 20 mg/kg once every 2 weeks for ≥4 years. Patients who switched to a different type of ERT during these 4 years must have received the 'new' ERT for at least 1 year and had a stable clinical course after the switch • Relatively stable clinical condition over the past year • Able to walk ≥150 m within 6 minutes (6MWT) • Non-invasive ventilation in supine position or, in case of no (non-invasive) ventilation,(forced) vital capacity (FVC) in sitting position: >55% of expected value and in supine position: >45% of expected value • Willing and able to adhere to the study procedures

Exclusion criteria 1

1. • Rapidly progressive muscle weakness. • Severely limited muscle strength almost requiring/requiring daily wheelchair use. • Requiring respiratory support (non-invasive/invasive ventilation) during the day while awake and seated, or being at high risk to require respiratory support (ventilation) either during the day or at night due to further deterioration of current pulmonary function. • Comorbidities which are expected to influence the primary outcome measures within the next 2 years.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Efficacy: - Muscle strength: manual muscle testing (MMT), hand-held dynamometry (HHD) - Muscle function: 6-minute walk test (6MWT), quick motor function test (QMFT) - Pulmonary function: forced vital capacity (FVC) in sitting and supine position, maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP) - Patient reported outcome measures (PROMs): modified Rasch-built Pompe-specific activity (mR-PAct) scale, SF-36 (QoL, quality of life)
2. Safety: - Vital signs: heart rate, blood pressure, respiratory rate - Weight - Assessment of treatment-emergent adverse events (TEAEs), including infusion associated reactions (IARs)

Investigational products

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

Test 4

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

Ina Barzel

Public contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Ina Barzel

Locations

1 EU/EEA country · 1 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 12 files

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

Application history

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