A Prospective Non-therapeutic Study in Patients Diagnosed With Niemann-Pick Disease Type C

Study Overview
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Brief Summary
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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.

Official Title
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A Prospective Non-therapeutic Study in Patients Diagnosed With Niemann-Pick Disease Type C in Order to Characterise the Individual Patient Disease Profile and Historic Signo-symptomatology Progression Pattern

Conditions
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Niemann-Pick Disease, Type C

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| NP-C Patients<br>NPC type 1 or 2 patients aged 2-18 years | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NP-C clinical disease severity | Change in NP-C Clinical Severity scale | at week 0 and week 24-28 | 
| Quality of life questionnaire (EQ-5D-Y) | Change in the Quality of life | at week 0 and week 24-28 | 
| Ultrasonographic evaluation of liver and spleen | Changes in the size and/or characteristics of the liver and spleen (assessed by ultrasound). | at week 0 and week 24-28 | 
| Oxysterol | Change in Oxysterol concentrations | at week 0 and week 24-28 | 
| NPC clinical symptoms | Change in NPC clinical symptoms | at week 0 and week 24-28 | 
| NPC protein | Change in NPC protein concentrations | at week 0 and week 24-28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Parameters | Adverse events (AEs) (disease related and treatment related), haematology, clinical chemistry, physical examination, vital signs and electrocardiogram (ECG). | at week 0 and week 24-28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NP-C, LSD, lysosomal storage disorder, lysosomal storage disease, NPC2, NPC1, Niemann-Pick Type C, Niemann-Pick,, Arimoclomol