A Multicenter Study of HGT-1110, an Enzyme Replacement Therapy Administered Intrathecally, in Children With Metachromatic Leukodystrophy (MLD) - Full Text View

Sponsor:	Shire Human Genetic Therapies, Inc.
Information provided by (Responsible Party):	Shire Human Genetic Therapies, Inc.
ClinicalTrials.gov Identifier:	NCT01510028

Purpose

The purpose of this study is to determine the safety of ascending doses of HGT-1110 administered by intrathecal (IT) injection for 40 weeks in children with metachromatic leukodystrophy (MLD).

Condition	Intervention	Phase
Leukodystrophy, Metachromatic	Biological: Recombinant human arylsulfatase A	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I/II, Multicenter, Randomized, Open-label, Controlled Dose Escalation Study of HGT-1110 Administered Intrathecally in Children With Metachromatic Leukodystrophy

Resource links provided by NLM:

Genetics Home Reference related topics: Chanarin-Dorfman syndrome cholesteryl ester storage disease leukoencephalopathy with vanishing white matter metachromatic leukodystrophy succinic semialdehyde dehydrogenase deficiency Help Me Understand Genetics

MedlinePlus related topics: Leukodystrophies

U.S. FDA Resources

Further study details as provided by Shire Human Genetic Therapies, Inc.:

Primary Outcome Measures:

Safety of IT HGT-1110 administration [ Time Frame: 40 weeks ] [ Designated as safety issue: Yes ]
Safety will be assessed by AEs (by type and severity), changes in clinical laboratory testing, electrocardiogram (ECG), vital signs, CSF chemistries and antibodies.

Secondary Outcome Measures:

Clinical activity of IT administration of HGT-1110 on gross motor function [ Time Frame: 40 weeks ] [ Designated as safety issue: No ]
Change from baseline in gross motor function
Serum Pharmacokinetic profile of HGT-1110 after single and repeated dose administration (weeks 0 and 38) [ Time Frame: 12 time points over 48 hours post-dose ] [ Designated as safety issue: No ]
- Cmax: maximal serum concentration
- Tmax: time to reach Cmax in plasma
- AUC: area under the curve
Concentrations of HGT-1110 in CSF [ Time Frame: 40 weeks ] [ Designated as safety issue: No ]
Concentrations of HGT-1110 in CSF prior to each IT administration

Estimated Enrollment:	20
Study Start Date:	December 2011
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Cohort 1 (10 mg) Cohort 1 (10 mg): 5 patients treated with HGT-1110 10 mg EOW by IT injection, with 2 no-treatment patients in Cohort 1.	Biological: Recombinant human arylsulfatase A Every other week (EOW) via an intrathecal drug delivery device (IDDD) Other Name: HGT-1110, rhASA
Cohort 2 (30 mg) Cohort 2 (30 mg): 5 patients treated with HGT-1110 30 mg EOW by IT injection, with 2 no-treatment patients in Cohort 2.	Biological: Recombinant human arylsulfatase A Every other week (EOW) via an intrathecal drug delivery device (IDDD) Other Name: HGT-1110, rhASA
Cohort 3 (100 mg) Cohort 3 (100 mg): 5 patients treated with HGT-1110 100 mg EOW by IT injection, with 1 no-treatment patient in Cohort 3.	Biological: Recombinant human arylsulfatase A Every other week (EOW) via an intrathecal drug delivery device (IDDD) Other Name: HGT-1110, rhASA

Detailed Description:

Metachromatic leukodystrophy (MLD) is an inherited, autosomal recessive disorder of lipid metabolism characterized by deficient activity of the lysosomal enzyme, arylsulfatase A (ASA). MLD is a rare disease that occurs in most parts of the world. The estimated overall incidence of the disease in the western world is approximately 1 in 100,000 live births that varies by geographic location. There are no approved therapies for MLD.

This is a multicenter, randomized, open-label, controlled, dose-escalation study designed to evaluate the safety of up to 3 dose levels (10, 30, or 100 mg) of HGT-1110 administered via an intrathecal drug delivery device (IDDD) every other week (EOW) for a total of 40 weeks (20 injections) to children with MLD. Up to 20 patients will be enrolled, with 15 of the 20 enrolled patients randomly selected to receive treatment with HGT-1110 and 5 patients to be untreated. Patients will be sequentially enrolled into 3 dose cohorts and each dose cohort will include treated and no treatment patients. Patient enrollment will be staggered in this study to facilitate adequate safety monitoring per dose cohort.

Eligibility

Ages Eligible for Study:	up to 8 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Confirmed diagnosis of metachromatic leukodystrophy by both:
- Arylsulfatase A (ASA) deficiency by assay in leukocytes AND
- Elevated sulfatide in urine
Appearance of the first symptoms of disease at or before 30 months of age.
Ambulatory at the time of screening. The minimum level of function required to meet this criterion is defined as the ability to stand up alone and walk forward 10 steps with one hand held.
Neurological signs of MLD must be present at the screening examination.
The patient and his/her parent/representative(s) must have the ability to comply with the clinical protocol.
Patient's parent or legally authorized representative(s) must provide written informed consent prior to performing any study-related activities. Study-related activities are any procedures that would not have been performed during normal management of the patient.

Exclusion Criteria:

History of hematopoietic stem cell transplantation.
The patient has any known or suspected hypersensitivity to anesthesia or is thought to be at an unacceptably high risk for anesthesia due to airway compromise or other conditions.
Any other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial.
The patient is enrolled in another clinical study that involves clinical investigations or use of any investigational product (drug or device) within 30 days prior to study enrollment or at any time during the study.
The patient is 8 years of age or older.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01510028

Locations

Denmark
Department of Clinical Genetics, Juliane Marie Centre, Copenhagen University Hospital
Copenhagen, Denmark, 2100

Sponsors and Collaborators

Shire Human Genetic Therapies, Inc.

Investigators

Study Director:

Eric Crombez, M.D.

Shire Human Genetic Therapies, Inc.

More Information

No publications provided

Responsible Party:	Shire Human Genetic Therapies, Inc.
ClinicalTrials.gov Identifier:	NCT01510028 History of Changes
Other Study ID Numbers:	HGT-MLD-070, 2011-002044-28
Study First Received:	December 14, 2011
Last Updated:	April 3, 2012
Health Authority:	Denmark: Danish Medicines Agency France: Afssaps - French Health Products Safety Agency Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Shire Human Genetic Therapies, Inc.:

Metachromatic Leukodystrophy(MLD)
Recombinant human arylsulfatase A (rhASA)
Intrathecal Drug Delivery Device (IDDD)

Additional relevant MeSH terms:

Leukodystrophy, Metachromatic
Hereditary Central Nervous System Demyelinating Diseases
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Sulfatidosis
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System

Leukoencephalopathies
Demyelinating Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on May 14, 2012