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

Sponsor

KemPharm Denmark A/S (Industry)

Overall Status

Completed

CT.gov ID

NCT02435030

Collaborator

(none)

Enrollment

Locations

Duration (Months)

2.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Niemann-Pick Disease, Type C

Study Design

Study Type:

Observational

Actual Enrollment :

35 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

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

Study Start Date :

Sep 1, 2015

Actual Primary Completion Date :

May 1, 2017

Actual Study Completion Date :

May 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
NP-C Patients NPC type 1 or 2 patients aged 2-18 years

Outcome Measures

Primary Outcome Measures

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).
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
NPC protein [at week 0 and week 24-28]
Change in NPC protein concentrations

Secondary Outcome Measures

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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	University Hospital Copenhagen (Rigshospitalet)	Copenhagen	Denmark	2100
2	CHU de Montpellier	Montpellier	France
3	Hôpital Trousseau	Paris	France
4	Villa Metabolica Mainz	Mainz	Germany	55131
5	Klinikum der Universistat, Munchen	Munich	Germany
6	Istituto Carlo Besta (Milano)	Milan	Italy	20133
7	Azienda Ospedaliera San Gerardo	Monza	Italy	20900
8	Università Federico II	Napoli	Italy	80138
9	Ospedale Pediatrico Bambino Gesù	Rome	Italy	00146
10	Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia"	Udine	Italy
11	The Children´s Memorial Istitute Warsaw	Warsaw	Poland	04-730
12	Hospital Vall D'Hebron	Barcelona	Spain	08035
13	Hospital Quirón	Zaragoza	Spain	50006
14	Inselspital, University Hospital Bern	Bern	Switzerland	3010
15	Birmingham Children's Hospital	Birmingham	United Kingdom	B4 6NH
16	Great Ormond Street Hospital	London	United Kingdom	WC1N 3JH