Primary Objective:The primary objective of this study is to establish the occurrence of neutralizing antibodies to SPK-GAA capsid in participants with LOPD on an enzyme replacement regimen. Secondary Objective:The secondary objectives of this study…
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Lysosomal storage disorder and neuromuscular disease
Research involving
Sponsors and support
Intervention
No registrations found.
Outcome measures
Primary outcome
• Occurrence and titer of SPK-GAA antibodies
Secondary outcome
• Anti-GAA binding antibodies
• Neutralizing antibodies to circulating GAA
• GAA activity
• GAA antigen level
Exploratory Endpoints:
• Current and retrospective laboratory evaluations: liver function tests,
Creatine Kinase (CK), albumin, infectious hepatitis serologies, bicarbonate,
Factor VII, Prothrombin time (PT), Partial Thromboplastin time (PTT), Thyroid
Stimulating Hormone (TSH), additional biomarkers of liver and muscle stress,
exploratory biomarker of lysosomal health Beta hexosaminidase (βHexo)
• Day 1 and historic (as available) FibroScan
• Current and retrospective chart review of ERT use
• Retrospective chart review (as available):
o Functional tests: 6-minute Walk Test (6MWT), Forced Vital Capacity
(FVC), other muscle function and pulmonary function tests
o MRI
o Muscle biopsy
o Liver FibroScan
o Liver Ultrasound
Background summary
Late onset Pompe disease (LOPD, glycogen storage disease type 2) patients
experience the consequences of intracellular glycogen
accumulation resulting from deficient activity of acid alpha glucosidase enzyme
(GAA). While many tissues may be affected, in LOPD the most frequent and
debilitating clinical consequences arise from the inability to normally clear
tissue glycogen from skeletal muscle including respiratory muscle, resulting in
myocyte death, loss of motor function and respiratory failure. Standard of care
enzyme replacement therapy (ERT) with intravenously infused recombinant human
GAA is poorly effective due to unfavorable pharmacokinetics and poor
bioavailability within tissues including skeletal muscle. Liver-directed gene
therapy may overcome the limitations of ERT and provide more effective disease
correction.
Study objective
Primary Objective:
The primary objective of this study is to establish the occurrence of
neutralizing antibodies to SPK-GAA capsid in participants with LOPD on an
enzyme replacement regimen.
Secondary Objective:
The secondary objectives of this study are to establish the occurrence of
anti-GAA binding antibodies, neutralizing antibodies to GAA, GAA activity and
GAA antigen levels in the usual care setting of LOPD participants on an enzyme
replacement regimen.
Exploratory Objectives:
The exploratory objectives will evaluate additional laboratory measures,
FibroScan, and historic MRI, muscle biopsy, liver imaging, muscle function, and
respiratory measures to assess baseline characteristics in participants with
LOPD on an enzyme replacement regimen.
Study design
This is a multi-center, low-interventional study with a retrospective component
in participants with LOPD. During a single study visit assessments including,
but not limited to liver health, neutralizing antibodies to SPK-GAA capsid,
neutralizing antibodies to GAA, anti-GAA binding antibodies, GAA activity and
GAA antigen levels will be performed. Additional information will be collected
to provide retrospective evaluations relating to muscle and liver inflammation
and/or injury. Historic data relating to Pompe disease will be collected from
medical records to further characterize LOPD.
Intervention
Not applicable
Study burden and risks
Total duration is 1 day.
Disadvantages of participating in the study: discomfort with blood collection,
time needed for the tests
3737 Market Street Suite 1300
Philadelphia PA 19104
US
3737 Market Street Suite 1300
Philadelphia PA 19104
US
Listed location countries
Age
Inclusion criteria
1. Provide written IC and authorization to use protected health information
(PHI) in accordance with national and local privacy regulation;
2. Male or females >=18 years of age;
3. Currently on ERT using regular recombinant human GAA infusions for at least
18 months prior to screening;
4. Documented history of clinically moderate late-onset Pompe disease. For
example:
a. Able to walk 150 meters on the 6-minute walk test (assistive devices
permitted)
b. Percentage of the predicted FVC >= 30% and <=80% in the upright position.
Exclusion criteria
1. History of HIV
2. Requires any invasive ventilation (other than BiPAP at night) or noninvasive
ventilation while awake and upright;
3. Previously received SPK-GAA
4. Previously dosed with any investigational or approved gene therapy product
at any time or treated with an investigational drug within the last 12 weeks
(vaccination studies are accepted)
5. Any concurrent clinically significant condition that would not allow the
potential participant to complete the Day 1 examinations, or other condition
that, in the opinion of the Investigator and/or Sponsor, makes the subject
unsuitable for participation in the study
6. Unable or unwilling to comply with the schedule of visits and/or study
assessments described in the clinical protocol
Design
Recruitment
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 |
---|---|
CCMO | NL68594.078.19 |