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

NCT02435030 | Completed

• 2 other identifiers: CT-ORZY-NPC-0012014-005194-37
• Study Type: observational
• Target: 35
• Locations: 8 countries
• Sites: 16

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.

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

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (1)

• Safety Parameters

  at week 0 and week 24-28

Study Arms (1)

NP-C Patients

NPC type 1 or 2 patients aged 2-18 years

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

NPC1 and NPC2 patients aged 2-18 years

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ZevraDenmark: lead

Study Sites (16)

University Hospital Copenhagen (Rigshospitalet)

Copenhagen, 2100, Denmark

Location

CHU de Montpellier

Montpellier, France

Location

Hôpital Trousseau

Paris, France

Location

Villa Metabolica Mainz

Mainz, 55131, Germany

Location

Klinikum der Universistat, Munchen

Munich, Germany

Location

Istituto Carlo Besta (Milano)

Milan, 20133, Italy

Location

Azienda Ospedaliera San Gerardo

Monza, 20900, Italy

Location

Università Federico II

Napoli, 80138, Italy

Location

Ospedale Pediatrico Bambino Gesù

Rome, 00146, Italy

Location

Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia"

Udine, Italy

Location

The Children´s Memorial Istitute Warsaw

Warsaw, 04-730, Poland

Location

Hospital Vall D'Hebron

Barcelona, 08035, Spain

Location

Hospital Quirón

Zaragoza, 50006, Spain

Location

Inselspital, University Hospital Bern

Bern, 3010, Switzerland

Location

Birmingham Children's Hospital

Birmingham, B4 6NH, United Kingdom

Location

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33228797 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma

MeSH Terms

Conditions

Niemann-Pick Disease, Type C; Lysosomal Storage Diseases

Condition Hierarchy (Ancestors)

Niemann-Pick Diseases; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Karl-Eugen Mengel

  Villa Metabolica, Mainz, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2015
• First Posted: May 6, 2015
• Study Start: September 1, 2015
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: May 18, 2017

Record last verified: 2017-05

Locations

ES (2); DK (1); IT (5); GB (2); FR (2); CH (1); PL (1); DE (2)