Primary ObjectiveThe primary objective of this study is to evaluate glycogen clearance in muscle tissue samples collected pre and post alglucosidase alfa treatment in patients with late-onset Pompe disease.Secondary ObjectivesThe secondary…
ID
Source
Brief title
Condition
- Inborn errors of metabolism
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of this study is: Percent reduction from baseline in
tissue glycogen content in muscle biopsy samples at Week 26.
Secondary outcome
The secondary endpoints of this study are:
- Tissue examination (to include assessment of glycogen distribution, muscle
fiber morphology, and lysosomal inclusions).
- Qualitative assessment of MR images for intact muscle and fatty replacement.
Background summary
Pompe disease is a rare, inherited disease caused by the deficiency of the
enzyme acid α-glucosidase. This enzyme normally breaks down sugar stored as
glycogen into glucose that can be used for energy by the body*s cells. If the
enzyme is not present, glycogen builds up in certain tissues, particularly the
muscles, including the heart and diaphragm (the main breathing muscle under the
lungs). The progressive build-up of glycogen causes a wide range of symptoms,
including an enlarged heart, breathing difficulties and muscle weakness. The
disease can appear at birth (the *infantile-onset* form) but also later in life
(the *late-onset* form).Alglucosidase alfa has been developed as an enzyme
replacement therapy for the treatment of Pompe disease and is registered since
2006.
Currently, there is no validated, sensitive non-invasive or minimally invasive
biomarker to monitor alglucosidase alfa pharmacodynamics in patients with
late-onset Pompe disease. Limited pathological data from late-onset patients
suggests significant patient to patient heterogeneity in terms of disease
severity. As a result, this study aims to explore the feasibility of using MRI
imaging and selective confirmatory muscle biopsy to characterize disease burden
and response to treatment with alglucosidase alfa in patients with late-onset
Pompe disease.
Study objective
Primary Objective
The primary objective of this study is to evaluate glycogen clearance in muscle
tissue samples collected pre and post alglucosidase alfa treatment in patients
with late-onset Pompe disease.
Secondary Objectives
The secondary objectives of this study are:
to characterize the disease burden in patients with late-onset Pompe disease
and explore imaging, histologic, and functional assessments in these patients.
to explore potential plasma or urine biomarkers relative to late-onset Pompe
disease and patient*s response to treatment with alglucosidase alfa.
Study design
Phase 4 prospective exploratory open-label multicenter study
Intervention
All patients receive every 2 weeks an intravenous infusion for 24 weeks of alfa
glucosidase alfa, a medication used for Pompe's disease.
Study burden and risks
Risks
• Functional testing: falls, shortness of breath, muscle soreness, and fatigue
• Repeat blood draws: momentary discomfort, bruising, excessive bleeding,
infection, fainting, and possible anemia
• Biopsy: soreness, infection, bleeding, bruising, and scarring at the biopsy
site
• MRI: claustrophobia in some patients, no physical risk
• Administration of medications:
About half of the infantile-onset patients who received the study drug in
clinical trials experienced infusion reactions to study drug. One third of the
late-onset patients experienced infusion reactions to study drug. Infusion
reactions occur at any time during, and within a few hours after the infusion
and are more likely with higher infusion rates. The majority of reactions were
assessed as mild to moderate and resolved spontaneously. In a previous study,
infusion reactions which were reported in at least 5 out of 100 late-onset
patients treated with study drug included headache, nausea, dizziness, hives,
rash, chest discomfort, vomiting, sweating, flushing (red in the face) and
blood pressure increased. Less commonly, approximately 2 out of 100 patients
can experience infusion reaction that can be life-threatening; this is known as
an anaphylactic reaction or severe allergic reaction.
Gooimeer 10
Naarden 1411 DD
NL
Gooimeer 10
Naarden 1411 DD
NL
Listed location countries
Age
Inclusion criteria
1.
The patient is willing and able to provide signed informed consent.
2.
The patient is >=18 years of age with confirmed acid α-glucosidase [GAA] enzyme deficiency from any tissue source and/or confirmed GAA gene mutations and without known cardiac hypertrophy.
3.
The patient is able to ambulate a certain distance without stopping and without an assistive device. Use of assistive device for community ambulation is appropriate.
4.
The patient has a certain forced vital capacity (FVC) in upright position.
5.
The patient, if female and of childbearing potential, must have a negative pregnancy test at baseline. Note: All female patients of childbearing potential and sexually mature males must agree to use a medically accepted method of contraception throughout the study.
Exclusion criteria
1.
The patient has had previous treatment with Enzyme Replacement Therapy.
2.
The patient is wheelchair dependent.
3.
The patient requires invasive-ventilation (non-invasive ventilation is allowed).
4.
The patient is participating in another clinical study using investigational treatment.
5.
The patient cannot submit to MRI examination because of a formal contraindication such as a pacemaker, implanted ferromagnetic metals, etc.
6.
The patient, in the opinion of the Investigator, is unable to adhere to the requirements of the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-020611-36-NL |
| ClinicalTrials.gov | NCT01288027 |
| CCMO | NL37650.078.11 |