Text Size

Multicenter Study of HGT-1110, Enzyme Replacement Therapy Administered Intrathecally, in Children With Metachromatic Leukodystrophy (MLD) (IDEAMLD)

This study is currently recruiting participants.
Verified December 2012 by Shire Human Genetic Therapies, Inc.
Sponsor:
Information provided by (Responsible Party):
Shire Human Genetic Therapies, Inc.
ClinicalTrials.gov Identifier:
NCT01510028
First received: December 14, 2011
Last updated: December 14, 2012
Last verified: December 2012
History of Changes
  Purpose

The purpose of this study is to determine the safety of ascending doses of HGT-1110 administered by intrathecal (IT) injection for 38 weeks (20 injections) 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: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Multicenter Open-label Dose Escalation Study of HGT-1110 Administered Intrathecally in Children With Metachromatic Leukodystrophy

Resource links provided by NLM:

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: 42 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: 18
Study Start Date: September 2012
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): 6 patients treated with HGT-1110 10 mg EOW by IT injection
 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): 6 patients treated with HGT-1110 30 mg EOW by IT injection
 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): 6 patients treated with HGT-1110 100 mg EOW by IT injection
 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, open-label, 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 38 weeks (20 injections, Weeks 0 to 38) to children with MLD. Up to 18 patients will be enrolled and will receive treatment of HGT-1110. Patients will be sequentially enrolled into 3 dose cohorts, 6 patients each. 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:

  1. Confirmed diagnosis of metachromatic leukodystrophy by both:

    • Arylsulfatase A (ASA) deficiency by assay in leukocytes AND
    • Elevated sulfatide in urine
  2. Appearance of the first symptoms of disease at or before 30 months of age.
  3. 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.
  4. The patient is less than 8 years of age at the time of enrollment.
  5. Neurological signs of MLD must be present at the screening examination.
  6. The patient and his/her parent/representative(s) must have the ability to comply with the clinical protocol.
  7. 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:

  1. History of hematopoietic stem cell transplantation.
  2. 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.
  3. Any other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial.
  4. The patient is enrolled in another clinical study that involves the use of any investigational product (drug or device) other than HGT-1110 or the IDDD used in this study within 30 days prior to study enrollment or at any time during the study.
  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 Recruiting
Copenhagen, Denmark, 2100
Contact: Christine Dali, MD         christine.dali@rh.regionh.dk    
Principal Investigator: Christine Dali, MD            
France
Hopital de Bicetre-Paris Sud Recruiting
Le Kremlin Bicetre, Ile-de-France, France, 94275
Contact: Caroline Sevin, MD         caroline.sevin@inserm.fr    
Principal Investigator: Caroline Sevin, MD            
Germany
Center for Pediatric Clinical Studies, Universitats-Kinderklinik Recruiting
Tubingen, Baden-Wuerttemberg, Germany, 72076
Contact: Joachim Riethmuller, MD         joachim.riethmuller@med.uni-tuebingen.de    
Principal Investigator: Joachim Riethmuller, MD            
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: December 14, 2012
Health Authority: Denmark: Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
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 22, 2013