A phase I/II randomised control study of OGT 918 in patients with Niemann-Pick type C disease

ISRCTN	ISRCTN26761144
DOI	https://doi.org/10.1186/ISRCTN26761144
ClinicalTrials.gov (NCT)	NCT00517153
Protocol serial number	OGT 918-007
Sponsor	Actelion Pharmaceuticals Ltd (Switzerland)
Funder	Actelion Pharmaceuticals Ltd (Switzerland)

Submission date: 05/07/2007
Registration date: 26/07/2007
Last edited: 02/10/2014

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Marc Patterson
Scientific

Division of Pediatric Neurology
Neurological Institute of New York, and
Columbia University College of Physicians and Surgeons
180 Fort Washington Avenue, HP-542
New York
NY 10032
United States of America

Phone	+1 (0)212 305 6038
Email	mcp73@columbia.edu

Study information

Primary study design	Interventional
Study design	Randomised controlled intervention study conducted at two centres
Secondary study design	Randomised controlled trial
Scientific title
Study objectives	Niemann-Pick type C disease is an inherited neurodegenerative disorder characterised by an intracellular lipid-trafficking defect with secondary accumulation of glycosphingolipids (GSLs). The purpose of the study was to evaluate the effects of miglustat (OGT 918) as a treatment for Niemann-Pick type C disease in adult, juvenile and paediatric patients over a 24-month treatment period. We hypothesised that patients in the treatment group would show slower rates of decline or stabilisation in one or more markers of the disease compared to the standard care group. The study was initially supported by Oxford GlycoSciences, the original manufacturer of miglustat (OGT 918). During the study the sponsor changed from Oxford GlycoSciences, a wholly-owned subsidiary of Celltech R&D Ltd, to Actelion Pharmaceuticals Ltd.
Ethics approval(s)	1. Centre 1: Salford and Trafford LREC, 24/12/2001, ref: 01266 2. Centre 2: Institutional Review Board of Columbia Presbyterian Medical Centre, 05/04/2002, ref: 14413
Health condition(s) or problem(s) studied	Niemann-Pick type C disease
Intervention	Patients in the juvenile/adult group (12 years or older) were randomised in a 2:1 ratio to either miglustat 200 mg three times daily orally (p.o.) for 12 months or standard symptomatic care (no study drug) as a control group. Both miglustat-treated and standard care groups received other concomitant medications for standard indications throughout the study. All children received miglustat in a dose adjusted according to Body Surface Area (BSA). Patients were assessed one week after commencing miglustat therapy and monthly thereafter with dose modification as clinically indicated.
Intervention type	Drug
Phase	Phase I/II
Drug / device / biological / vaccine name(s)	Miglustat (OGT 918)
Primary outcome measure(s)	Primary efficacy endpoint: change from baseline in Horizontal Saccadic Eye Movement (HSEM)-alpha (a measure of HSEM velocity) at 12 months or last available value
Key secondary outcome measure(s)	Secondary efficacy endpoints: 1. HSEM-beta 2. Assessments of swallowing (at screening and months 6 and 12; the assessor evaluated the patient's swallowing ability with prespecified substances, using a five-degree category scale from 'no problems of swallowing' to 'could not swallow the substance at all') 3. Auditory acuity (part of neurological examination at screening and months 3, 6, 9 and 12) 4. Ambulatory ability (standard ambulation index; part of neurological examination at screening and months 3, 6, 9 and 12) 5. Cognition (Mini Mental Status Examination [MMSE]; at screening and months 3, 6, 9, 12)
Completion date	30/04/2004

Eligibility

Participant type(s)	Patient
Age group	Other
Sex	All
Target sample size at registration	41
Key inclusion criteria	1. Juveniles and adults (12 years and over) and paediatric patients aged 4 - 11 years 2. Patients with Niemann-Pick type C disease confirmed by reduced cholesterol esterification and abnormal filipin staining in cultured fibroblasts 3. Capable of cooperating with physical examination and other testing
Key exclusion criteria	1. Clinically significant diarrhoea (greater than three liquid stools per day for more than 7 days without definable cause) within 3 months before enrolment 2. Significant gastrointestinal disorders or other intercurrent illnesses
Date of first enrolment	01/03/2003
Date of final enrolment	30/04/2004

Locations

Countries of recruitment

United Kingdom
United States of America

Study participating centre

Division of Pediatric Neurology

New York
NY 10032
United States of America

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/09/2007		Yes	No