Evaluate the clinical progression in patients with MPS IIIA who are untreated with any investigational product and to obtain standardized assessments: neurocognitive, behavioural, sleep-wake habits and effect of MPS IIIA on the quality of life of…
ID
Source
Brief title
Condition
- Chromosomal abnormalities, gene alterations and gene variants
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Study endpoints:
1. The change from baseline in cognitive function using the Bayley scales of
infant and toddler development third edition
2. The change from baseline in the adaptive behaviour composite standard score
as measured by the Vineland Adaptive Behaviour Scales, second edition -
Expanded interview (VABS-II)
3. Longitudinal description of sleep disturbances in MPSIIIA children using the
Children*s sleep habits questionnaire, diary and Actigraphy
4. A description of the patient and parents quality of life
5. A description of the adverse events
6. The change from baseline in total cortical grey matter volume will be
recorded, ONLY if brain MRI is standard of care
7. Concentrations of biomarkers will be studied, ONLY if drawing blood/lumbar
puncture is standard of care
Secondary outcome
Non Applicable
Background summary
Sanfilippo syndrome, or Mucopolysaccharidosis type III (MPS III), is a rare
lysosomal disease. MPS IIIA is caused by an autosomal recessive genetic defect
of a lysosomal sulfamidase. MPS IIIA is a rare disease with an estimated
prevalence of approximately 1 per 100,000 live birth. Clinical manifestations
are predominantly characterized by severe neurodegenerative features combined
with relatively milder somatic symptoms. It leads to an extremely deteriorated
quality of life and is a particularly devastating disease both for those
affected and their families. There is variability in the disease phenotype but
not a fully predictive genotype-phenotype correlation. A majority (70%) of
patients are reported to have the severe classical form of MPS IIIA. The median
age of death is about 15 years of age .
The most commonly reported cause of death is pneumonia. There is currently no
disease altering treatment for MPSIIIA. Lysogene is developing a gene therapy
intended to be a one-time treatment for MPS IIIA. Lysogene*s gene therapy route
of administration is direct delivery of the vector to the CNS. This may be one
of the most efficient methods to treat neurological pathologies of LSDs.
Lysogene is planning a multi-centre pivotal phase II/III study in around 20
patients in Europe and the USA.
For more information, you can go to the protocol section "Background" p14/66.
Study objective
Evaluate the clinical progression in patients with MPS IIIA who are untreated
with any investigational product and to obtain standardized assessments:
neurocognitive, behavioural, sleep-wake habits and effect of MPS IIIA on the
quality of life of patients and their families. To assess the cross-reactive
immunological material status of MPSIIIA patients.
Study design
This is a European, multi-centre, prospective, descriptive cohort study to
detail the natural course of MPSIIIA via standardized clinical, biochemical,
neurocognitive, developmental, and behavioural measures.
This study will have up to 6 onsite visits as follows:
Screening
Baseline (assessment day 0)
Assessment: 6-month contact (+/-14 days) from baseline
Assessment: 12-month contact (+/-14 days) from baseline
Assessment: 18-month contact (+/-14 days) from baseline
Assessment: 24-month contact (+/-14 days) or end of study visit from baseline
Study burden and risks
Potential benefits (protocol p15/66): Participants will have access to routine
metabolic follow up that may improve medical care. They will have
neuropsychological testing performed that may assist in educational
planning.This natural history should provide important information about the
clinical course of MPS IIIA. The information to be learned should be useful in
understanding future therapeutic effects.
Jacques Dulud 18-20
Neuilly sur Seine 92200
FR
Jacques Dulud 18-20
Neuilly sur Seine 92200
FR
Listed location countries
Age
Inclusion criteria
* Documented MPS IIIA diagnosis.
* Children up to and including 9 years of age.
* The patient is sufficiently able, in the opinion of the Investigator, to adhere to the study visit schedule and other protocol requirements.
* The patient's parent(s) or legal guardian(s) has signed written informed consent, according to the local regulations and after all relevant aspects of the study have been explained and discussed.
Exclusion criteria
* The patient is participating in a clinical trial of any potential disease-modifying investigational medicinal product or taking high dose (>100 mg/kg/day) synthetic Genistein (patients on low dose or naturally derived genistein can be included in this study).
* The patient has received a hemapoietic stem cell or bone marrow transplant or gene therapy.
* The patient has received enzyme replacement therapy.
* Homozygous or compound heterozygous for the S298P mutation or the investigator and/or trial steering committee considers the patient not to have the classical severe form of MPS IIIA.
* Individuals with rare and unrelated serious comorbidities e.g. Down syndrome, intraventricular haemorrhage in the new-born period, or extreme low birth weight (<1500 grams).
* Visual or hearing impairment sufficient, in the clinical judgment of the investigator, to preclude cooperation with neurodevelopmental testing. Use of hearing aids is permitted.
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 | NL56624.018.16 |
| Other | The protocol will be registered on clinicaltrials.gov |