This study has been transitioned to CTIS with ID 2024-513859-33-00 check the CTIS register for the current data. The overall objective is to assess efficacy, safety, pharmacokinetic (PK), pharmacodynamics (PD) of avalglucosidase alfa in male and…
ID
Source
Brief title
Condition
- Metabolic and nutritional disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the effect of avalglucosidase alfa treatment on survival and
invasive ventilator-free survival of IOPD participants after 52 weeks of
treatment.
Secondary outcome
To determine the effect of avalglucosidase alfa treatment on survival and
invasive ventilator-free survival at 12 and 18 months of age, as well the
change in left ventricular mass Z-score (LVM Zscore); Alberta Infant Motor
Scale (AIMS) score; body length, body weight, and head circumference Z-scores;
and urinary Hex4 at Week 52
To determine safety, tolerability, and immunogenicity of avalglucosidase alfa
To determine the PK profile at Week 12 and Week 52
Background summary
Pompe Disease is a rare, inherited disease caused by the deficiency of the
enzyme acid alfa-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
muscles including the heart and the diaphragm (the main breathing muscle under
the lungs). The progressive build up of glycogen causes a wide range of
symptoms, including an enlarged heart and breathing difficulties and muscle
weakness. The disease can appear at birth (the infantile onset form) but also
later in life (the late onset form).
Study objective
This study has been transitioned to CTIS with ID 2024-513859-33-00 check the CTIS register for the current data.
The overall objective is to assess efficacy, safety, pharmacokinetic (PK),
pharmacodynamics (PD) of avalglucosidase alfa in male and female
participants less than or equal to 6 months of age with IOPD.
Study design
This is a single group, treatment, Phase 3, open-label study to assess
efficacy, safety, pharmacokinetic (PK), pharmacodynamics (PD) of
avalglucosidase alfa in male and female participants less than or equal to 6
months of age with IOPD.
The study will also include up to 2 participants 7 to 12 months of age to be
evaluated combined and seperately with participants <6 months of age.
Following a screening period of up to 4 weeks, all participants will be treated
with avalglucosidase alfa 40 mg/kg qow for 52 weeks for the PAP and will
continue to receive treatment in the subsequent 52-week study ETP. This will be
followed by an ELTP up to 104 weeks plus the 4-week follow-up for a total study
duration of up to 4.08 years.
Intervention
Biweekly intravenous injections with avalglucosidase alfa in a dose of 40
mg/kg. This can be increased to weekly dosing of 40 mg/ kg is needed for safety
or efficacy reason,
Study burden and risks
Risks
- Functional testing: Fatigue
- Blood draws: momentary discomfort, swelling, bruising, infection, bleeding,
pain, light-heaed, redness at injection site. If possible a central venous
catheter will be placed for blood collection to reduce pain by needle sticks.
- Elecrocardiogram (ECG): momentary discomfort
- Administration of medication
Infusion associated reaction occurred at patients receiving avalglucosidase
alfa:
- Very common (affecting more than 1 in 10 people):
headache, generalized rash, muscle pain, nausea, diarrhea
- Common, frequent (affecting up to 1 in 10 people) :
redness, cough, dizziness, difficulty breathing, acid reflux, chest pressure,
decreased blood pressure, itching, feeling tired, feeling hot, feeling cold or
having chills, swelling of face, lip and tongue, arms or legs, throat
tightness**infusion site reaction**abnormal breathing sounds**abnormal heart
beating**redness in the face
Other possible side effects seen in both infantile- and/or late-onset patients
treated with avalglucosidase (affecting more than 1 in 10 people):
nasopharyngitis, headache, diarrhoea, back pain, fall, nausea, pain in
extremity, upper respiratory tract infection, rash, arthralgia, influenza,
fatigue, vomiting, myalgia, muscle spasms, pyrexia, dizziness, musculoskeletal
pain, pruritus, abdominal pain, contusion
Paasheuvelweg 25
Amsterdam 1105 BP
NL
Paasheuvelweg 25
Amsterdam 1105 BP
NL
Listed location countries
Age
Inclusion criteria
- Participants must have confirmed diagnosis of infantile-onset Pompe disease
defined as:
the presence of 2 lysosomal acid α-glucosidase (GAA) pathogenic variants and a
documented GAA deficiency from blood, skin, or muscle tissue; or the presence
of 1 GAA
pathogenic variant and a documented GAA deficiency from blood, skin and muscle
tissue
in 2 separate samples (from either 2 different tissues or from the same tissue
but at 2
different sampling dates).
- Participants must have established cross-reactive immunological material
(CRIM) status
available prior to enrollment.
- Participants must have cardiomyopathy at the time of diagnosis: ie, LVMI
equivalent to
mean age specific LVMI
+1 standard deviation for participants diagnosed by newborn screening or sibling
screening;
+2 standard deviation for participants diagnosed by clinical evaluation.
- Parents or legally authorized representative(s) must be capable of giving
signed
informed consent.
Exclusion criteria
- Participants with symptoms of respiratory insufficiency, including any
ventilation use
(invasive or noninvasive) at the time of enrollment.
- Participants with major congenital abnormality.
- Participants with clinically significant organic disease (with the exception
of symptoms
relating to Pompe disease).
- Participant received enzyme-replacement therapy (ERT) with recombinant human
acid α
glucosidase (rhGAA) from any source.
- Participant who has previously been treated in any clinical trial of
avalglucosidase alfa.
- Participant not suitable for participation, whatever the reason, as judged by
the
Investigator, including medical or clinical conditions, or participants
potentially at risk of
noncompliance to study procedures.
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 |
|---|---|
| EU-CTR | CTIS2024-513859-33-00 |
| EudraCT | EUCTR2020-004686-39-NL |
| ClinicalTrials.gov | NCT04910776 |
| CCMO | NL76557.078.21 |