A Prospective Non-therapeutic Study in Patients Diagnosed With Niemann-Pick Disease Type C
- Conditions
- Niemann-Pick Disease, Type C
- Registration Number
- NCT02435030
- Lead Sponsor
- ZevraDenmark
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 35
- 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.
- 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.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method NP-C clinical disease severity at week 0 and week 24-28 Change in NP-C Clinical Severity scale
Quality of life questionnaire (EQ-5D-Y) at week 0 and week 24-28 Change in the Quality of life
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).
NPC clinical symptoms at week 0 and week 24-28 Change in NPC clinical symptoms
Oxysterol at week 0 and week 24-28 Change in Oxysterol concentrations
NPC protein at week 0 and week 24-28 Change in NPC protein concentrations
- Secondary Outcome Measures
Name Time Method 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).
Trial Locations
- Locations (16)
Great Ormond Street Hospital
🇬🇧London, United Kingdom
University Hospital Copenhagen (Rigshospitalet)
🇩🇰Copenhagen, Denmark
Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia"
🇮🇹Udine, Italy
CHU de Montpellier
🇫🇷Montpellier, France
Hôpital Trousseau
🇫🇷Paris, France
Villa Metabolica Mainz
🇩🇪Mainz, Germany
Klinikum der Universistat, Munchen
🇩🇪Munich, Germany
Hospital Quirón
🇪🇸Zaragoza, Spain
Hospital Vall D'Hebron
🇪🇸Barcelona, Spain
Istituto Carlo Besta (Milano)
🇮🇹Milan, Italy
Università Federico II
🇮🇹Napoli, Italy
The Children´s Memorial Istitute Warsaw
🇵🇱Warsaw, Poland
Birmingham Children's Hospital
🇬🇧Birmingham, United Kingdom
Azienda Ospedaliera San Gerardo
🇮🇹Monza, Italy
Ospedale Pediatrico Bambino Gesù
🇮🇹Rome, Italy
Inselspital, University Hospital Bern
🇨🇭Bern, Switzerland