Clinical trial NCT02435030: A Prospective Non-therapeutic Study in Patients Diagnosed With Niemann-Pick Disease Type C
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 type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Niemann-Pick Disease, Type C
Keywords: NP-C
LSD
lysosomal storage disorder
lysosomal storage disease
NPC2
NPC1
Niemann-Pick Type C
Niemann-Pick,
Arimoclomol
Lead sponsor: ZevraDenmark
Sponsor class: INDUSTRY
First posted: 2015-05-06
Enrollment: 35
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: NPC1 and NPC2 patients aged 2-18 years

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.


Eligibility criteria: 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.

Primary outcomes:
measure: NP-C clinical disease severity
timeFrame: at week 0 and week 24-28
measure: Quality of life questionnaire (EQ-5D-Y)
timeFrame: at week 0 and week 24-28
measure: Ultrasonographic evaluation of liver and spleen
timeFrame: at week 0 and week 24-28
measure: Oxysterol
timeFrame: at week 0 and week 24-28
measure: NPC clinical symptoms
timeFrame: at week 0 and week 24-28
measure: NPC protein
timeFrame: at week 0 and week 24-28
Secondary outcomes:
measure: Safety Parameters
timeFrame: at week 0 and week 24-28
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: University Hospital Copenhagen (Rigshospitalet)
city: Montpellier
country: France
facility: CHU de Montpellier
city: Paris
country: France
facility: Hôpital Trousseau
city: Mainz
country: Germany
facility: Villa Metabolica Mainz
city: Munich
country: Germany
facility: Klinikum der Universistat, Munchen
city: Milan
country: Italy
facility: Istituto Carlo Besta (Milano)
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo
city: Napoli
country: Italy
facility: Università Federico II
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Gesù
city: Udine
country: Italy
facility: Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia"
city: Warsaw
country: Poland
facility: The Children´s Memorial Istitute Warsaw
city: Barcelona
country: Spain
facility: Hospital Vall D'Hebron
city: Zaragoza
country: Spain
facility: Hospital Quirón
city: Bern
country: Switzerland
facility: Inselspital, University Hospital Bern
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
Study officials:
affiliation: Villa Metabolica, Mainz, Germany
name: Karl-Eugen Mengel
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mengel E, Bembi B, Del Toro M, Deodato F, Gautschi M, Grunewald S, Gronborg S, Heron B, Maier EM, Roubertie A, Santra S, Tylki-Szymanska A, Day S, Symonds T, Hudgens S, Patterson MC, Guldberg C, Ingemann L, Petersen NHT, Kirkegaard T, I Dali C. Clinical disease progression and biomarkers in Niemann-Pick disease type C: a prospective cohort study. Orphanet J Rare Dis. 2020 Nov 23;15(1):328. doi: 10.1186/s13023-020-01616-0.