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

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

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.

Study Overview

• Status: Completed
• Conditions: Niemann-Pick Disease, Type C

• Study Type: Observational
• Enrollment (Actual): 35

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • University Hospital Copenhagen (Rigshospitalet)
• France
  • Montpellier, France
    • CHU de Montpellier
  • Paris, France
    • Hopital Trousseau
• Germany
  • Mainz, Germany, 55131
    • Villa Metabolica Mainz
  • Munich, Germany
    • Klinikum der Universistat, Munchen
• Italy
  • Milan, Italy, 20133
    • Istituto Carlo Besta (Milano)
  • Monza, Italy, 20900
    • Azienda Ospedaliera San Gerardo
  • Napoli, Italy, 80138
    • Università Federico II
  • Rome, Italy, 00146
    • Ospedale Pediatrico Bambino Gesù
  • Udine, Italy
    • Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia"
• Poland
  • Warsaw, Poland, 04-730
    • The Children´s Memorial Istitute Warsaw
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Zaragoza, Spain, 50006
    • Hospital Quirón
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital, University Hospital Bern
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Children's Hospital
  • London, United Kingdom, WC1N 3JH
    • Great Ormond Street Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

NPC1 and NPC2 patients aged 2-18 years

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
NP-C Patients; NPC type 1 or 2 patients aged 2-18 years

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: KemPharm Denmark A/S
• Investigators: Principal Investigator: Karl-Eugen Mengel, Villa Metabolica, Mainz, Germany

Publications and helpful links

General Publications

• 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. Erratum In: Orphanet J Rare Dis. 2021 Jun 1;16(1):246.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: April 22, 2015
• First Submitted That Met QC Criteria: April 30, 2015
• First Posted (Estimate): May 6, 2015

Study Record Updates

• Last Update Posted (Actual): May 18, 2017
• Last Update Submitted That Met QC Criteria: May 17, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: LSD; NPC1; Niemann-Pick Type C; lysosomal storage disorder; lysosomal storage disease; NPC2; NP-C; Arimoclomol; Niemann-Pick,
• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Lymphatic Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Genetic Diseases, Inborn; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Dementia; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Language Disorders; Communication Disorders; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Speech Disorders; Frontotemporal Lobar Degeneration; Aphasia; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain; Niemann-Pick Diseases; Niemann-Pick Disease, Type A; Niemann-Pick Disease, Type C
• Other Study ID Numbers: CT-ORZY-NPC-001; 2014-005194-37 (EudraCT Number)