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

NCT ID: NCT02435030

Last Updated: 2017-05-18

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 35 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2017-05-31

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

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

NP-C Patients

NPC type 1 or 2 patients aged 2-18 years

No interventions assigned to this group

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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ZevraDenmark

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karl-Eugen Mengel

Role: PRINCIPAL_INVESTIGATOR

Villa Metabolica, Mainz, Germany

Locations

University Hospital Copenhagen (Rigshospitalet)

Copenhagen, , Denmark

CHU de Montpellier

Montpellier, , France

Hôpital Trousseau

Paris, , France

Villa Metabolica Mainz

Mainz, , Germany

Klinikum der Universistat, Munchen

Munich, , Germany

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, , Italy

The Children´s Memorial Istitute Warsaw

Warsaw, , Poland

Hospital Vall D'Hebron

Barcelona, , Spain

Hospital Quirón

Zaragoza, , Spain

Inselspital, University Hospital Bern

Bern, , Switzerland

Birmingham Children's Hospital

Birmingham, , United Kingdom

Great Ormond Street Hospital

London, , United Kingdom

Countries

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

References

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.

Reference Type: DERIVED

PMID: 33228797 (View on PubMed)

Other Identifiers

2014-005194-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CT-ORZY-NPC-001

Identifier Type: -

Identifier Source: org_study_id