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

Niemann-Pick Disease, Type C Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02435030
• Other study ID #: CT-ORZY-NPC-001
• Secondary ID: 2014-005194-37
• Status: Completed
• Phase: N/A
• First received: April 22, 2015
• Last updated: May 17, 2017
• Start date: September 2015
• Est. completion date: May 2017

Study information

• Verified date: May 2017
• Source: Orphazyme
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: May 2017
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Aphasia, Primary Progressive
• Frontotemporal Dementia
• Niemann-Pick Disease, Type C
• Niemann-Pick Diseases
• Pick Disease of the Brain

Locations

Country	Name	City	State
Denmark	University Hospital Copenhagen (Rigshospitalet)	Copenhagen
France	CHU de Montpellier	Montpellier
France	Hôpital Trousseau	Paris
Germany	Villa Metabolica Mainz	Mainz
Germany	Klinikum der Universistat, Munchen	Munich
Italy	Istituto Carlo Besta (Milano)	Milan
Italy	Azienda Ospedaliera San Gerardo	Monza
Italy	Università Federico II	Napoli
Italy	Ospedale Pediatrico Bambino Gesù	Rome
Italy	Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia"	Udine
Poland	The Children´s Memorial Istitute Warsaw	Warsaw
Spain	Hospital Vall D'Hebron	Barcelona
Spain	Hospital Quirón	Zaragoza
Switzerland	Inselspital, University Hospital Bern	Bern
United Kingdom	Birmingham Children's Hospital	Birmingham
United Kingdom	Great Ormond Street Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Orphazyme

Countries where clinical trial is conducted

Denmark,  France,  Germany,  Italy,  Poland,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	NP-C clinical disease severity	Change in NP-C Clinical Severity scale	at week 0 and week 24-28
Primary	Quality of life questionnaire (EQ-5D-Y)	Change in the Quality of life	at week 0 and week 24-28
Primary	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
Primary	Oxysterol	Change in Oxysterol concentrations	at week 0 and week 24-28
Primary	NPC clinical symptoms	Change in NPC clinical symptoms	at week 0 and week 24-28
Primary	NPC protein	Change in NPC protein concentrations	at week 0 and week 24-28
Secondary	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