Niemann-Pick Disease, Type C
Conditions
Keywords
NP-C, LSD, lysosomal storage disorder, lysosomal storage disease, NPC2, NPC1, Niemann-Pick Type C, Niemann-Pick,, Arimoclomol
Brief summary
This is a prospective non-therapeutic observational study in NP-C patients. The aim is to characterize the individual patient disease progression profile through the historical and 6 months prospective evaluation of clinical, imaging, biological(biomarkers) and quality of life data. Patients will be offered enrollment into a Phase II/III study on arimoclomol at the end of the study.
Interventions
None listed
Sponsors
ZevraDenmark
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent (and assent if appropriate to local laws and regulations) prior to any study-related procedures; * Males and females aged from 2 years to 18 years and 11 months; * Patients of any ethnic background will be eligible for this study; * Patient weight ≥15th percentile of body mass index (BMI) for age according to the World Health Organisation (WHO) standards; * Diagnosis of Niemann Pick disease Type C (NP-C), either NPC1 or NPC2; * NP-C diagnosis genetically confirmed (deoxyribonucleic acid \[DNA\] sequence analysis); * Both NPC1 and NPC2 patients are eligible; * Presenting at least one neurological symptom of the disease (for example, but not limited to, hearing loss, vertical supranuclear gaze palsy, ataxia, dementia, dystonia, seizures, dysarthria, or dysphagia); * Ability to walk either independently or with assistance; * Ability to travel to the corresponding clinical trial site repeatedly (every 6 months) for evaluation and follow-up; * Treated or non-treated with miglustat; * If a patient is under prescribed treatment with miglustat, it has to be under stable dose of the medication for ≥ 3 continuous months prior to inclusion in the study; * Sexually active patients must be willing and able to use an adequate method of contraception throughout the study, for example: diaphragm + spermicide; intrauterine contraceptive device; oral contraceptives; implant; injection of a progestogen medication; * Ability to comply with the protocol-specified procedures/evaluations and scheduled visits; * Willing to participate in all aspects of trial design including serial blood sampling, skin biopsies and imaging (ultrasonography) collections.
Exclusion criteria
* No written informed consent obtained from the patient or their parent(s)/legal guardian(s) (and assent if appropriate to local laws and regulation) before any study related procedures; * Recipient of a liver transplant or planned liver transplantation; * Patients with uncontrolled severe epileptic seizures period (at least 3 consecutive severe epileptic seizures that required medication) within 2 months prior to the written consent. This includes patients with ongoing seizures that are not stable in frequency or type or duration over a 2 month period prior to enrollment, requiring change in dose of antiepileptic medication (other than adjustment for weight) over a 2 month period prior to enrollment, or requiring 3 or more antiepileptic medications to control seizures; * Neurologically asymptomatic patients; * Severe liver insufficiency (defined as hepatic laboratory parameters, aspartate transaminase \[AST\] and alanine transaminase \[ALT\] greater than three-times the upper limit of normal for age and gender; * Severe renal insufficiency, with serum creatinine level greater than 1.5 times the upper limit of normal ; * Severe manifestations of NP-C disease that would interfere with the patient's ability to comply with the requirements of this protocol; * In the opinion of the Investigator, the patient's clinical condition does not allow for the required blood collection and/or skin biopsies as per the protocol-specified procedures; * Treatment with any IMP within 4 weeks prior to the study enrollment; * Treatment with any IMP during the study in an attempt to treat NP-C; * Current participation in another trial is not permitted unless it is a non-interventional study and the sole purpose of the trial is for long-term follow up/survival data (registry); * Patients will be excluded if there is a confirmed risk linked to the MRI procedure to be performed in the subsequent therapeutic interventional study \[i.e.: implanted cardiac pacemaker or implantable cardioverter defibrillator, implanted neural pacemakers, cochlear implants, implanted metallic foreign bodies in the eye or CNS (such as a CNS aneurysmal clip), any form of implanted wire or metal device that may concentrate radio frequency fields and/or confirmed history of unexpected serious adverse reaction to sedation or anesthesia (if sedation is necessary)\]; * Patients will be excluded if there is a confirmed risk linked to the skin punch biopsy procedure like severe thrombocytopaenia, at investigator's discretion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ultrasonographic evaluation of liver and spleen | at week 0 and week 24-28 | Changes in the size and/or characteristics of the liver and spleen (assessed by ultrasound). |
| Quality of life questionnaire (EQ-5D-Y) | at week 0 and week 24-28 | Change in the Quality of life |
| NP-C clinical disease severity | at week 0 and week 24-28 | Change in NP-C Clinical Severity scale |
| NPC protein | at week 0 and week 24-28 | Change in NPC protein concentrations |
| Oxysterol | at week 0 and week 24-28 | Change in Oxysterol concentrations |
| NPC clinical symptoms | at week 0 and week 24-28 | Change in NPC clinical symptoms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety Parameters | at week 0 and week 24-28 | Adverse events (AEs) (disease related and treatment related), haematology, clinical chemistry, physical examination, vital signs and electrocardiogram (ECG). |
Countries
Denmark, France, Germany, Italy, Poland, Spain, Switzerland, United Kingdom
Outcome results
None listed