Long-term safety and pharmacokinetics (PK) of neoGAA
ID
Source
Brief title
Condition
- Inborn errors of metabolism
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To eveluate the long term safety of neoGAA in Pompe disease patients
Secondary outcome
To evaluate ECG, Immunogenicity assessments, PK, skeletal muscle glycogen
content, skeletal muscle glycogen content, urinary Hex4, plasma analysis of
circulating mRNA and micro RNA, serum analyses of skeletal muscle RNA
expression
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). NeoGAA is a form of enzyme replacement therapy (ERT).
It is a recombinant form of the naturally occurring enzyme (GAA) that is
missing in patients with Pompe disease.
Study objective
Long-term safety and pharmacokinetics (PK) of neoGAA
Study design
open-label, multicenter
Intervention
5 mg/kg, 10 mg/kg or 20 mg/kg of body weight neoGAA every other week (qow) for
a maximum of 6 years.
The protocol amendment 3 was made as results from the NEO-1 are available. All
patients will be switched to 20 mg/kg if they can tolerate the dose.
Study burden and risks
Alglucosidase alfa (tradenames Lumizyme or Myozyme) is an ERT drug for Pompe
disease for which side effects are known. It is anticipated that the
side-effects for neoGAA will be similar to those for alglucosidase alfa. The
majority of reactions with alglucosidase alfa in late-onset Pompe disease
patients were assessed as mild to moderate and disappeared on their own. In a
previous study with alglucosidase alfa, infusion reactions which were reported
in at least 5 out of 100 lateonset patients treated 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. A small
number of patients developed anaphylactic shock with alglucosidase alfa, and in
the infantile-onset Pompe disease patient population a few patients experienced
a brief episode of cardiac arrest during alglucosidase alfa infusion that
required life-support measures. Severe allergic, anaphylactic reactions can
include symptoms such as difficulty breathing, throat tightness, swelling of
the face, lips or tongue, a significant drop in blood pressure and hives or
rashes. Most patients have been successfully managed and have been able to
continue treatment with the alglucosidase alfa. 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.
Paasheuvelweg 25
Amsterdam 1105BP
NL
Paasheuvelweg 25
Amsterdam 1105BP
NL
Listed location countries
Age
Inclusion criteria
Patients with Pompe disease who previously completed a neoGAA study.
Exclusion criteria
* The patient is concurrently participating in another clinical study using
investigational treatment.
* The patient, in the opinion of the Investigator, is unable to adhere to the
requirements of the study.
* The patient has clinically significant organic disease (with the exception of
symptoms relating to Pompe disease), including clinically significant
cardiovascular, hepatic, pulmonary, neurologic, or renal disease, or other
medical condition, serious intercurrent illness, or extenuating circumstance
that, in the opinion of the Investigator, precludes participation in the study
or potentially decreases survival.
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 | EUCTR2013-003321-28-NL |
| ClinicalTrials.gov | NCT02032524 |
| CCMO | NL49423.078.14 |