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

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Shire Identifier:
First received: December 14, 2011
Last updated: May 18, 2015
Last verified: May 2015

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
Metachromatic Leukodystrophy
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:

Further study details as provided by Shire:

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: August 2012
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 (10 mg)
6 patients treated with HGT-1110 10 mg EOW by IT injection
Biological: Recombinant human arylsulfatase A
Other Name: HGT-1110, rhASA
Experimental: Cohort 2 (30 mg)
6 patients treated with HGT-1110 30 mg EOW by IT injection
Biological: Recombinant human arylsulfatase A
Other Name: HGT-1110, rhASA
Experimental: Cohort 3 (100 mg)
6 patients treated with HGT-1110 100 mg EOW by IT injection
Biological: Recombinant human arylsulfatase A
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.


Ages Eligible for Study:   up to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 walk forward 10 steps with one hand held.
  4. The patient is less than 12 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.
  5. The patient is pregnant or breastfeeding.
  6. The patient has a condition that is contraindicated as described in the SOPH-A-PORT Mini S IDDD Instructions for Use, including:

    • The patient has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT Mini S device.
    • The patient's body size is too small to support the size of the SOPH-A-PORT Mini S Access Port, as judged by the Investigator.
    • The patient has a known or suspected local or general infection.
    • The patient is at risk of abnormal bleeding due to a medical condition or therapy.
    • The patient has one or more spinal abnormalities that could complicate safe implantation or fixation.
    • The patient has a functioning CSF shunt device.
    • The patient has shown an intolerance to an implanted device
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01510028

The Children's Hospital at Westmead
Westmead, Australia, 2145
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande Do Sul, Brazil, 90035-003
København, Denmark, 2100
Hopital de Bicetre
Le Kremlin Bicetre, Ile-de-France, France, 94275
Center for Pediatric Clinical Studies
Tubingen, Baden-Wuerttemberg, Germany, 72076
Osaka University Hospital
Suita, Japan, 565-0871
Sponsors and Collaborators
Study Director: Anna wijatyk, M.D. Shire
  More Information

No publications provided

Responsible Party: Shire Identifier: NCT01510028     History of Changes
Other Study ID Numbers: HGT-MLD-070, 2011-002044-28, U1111-1153-1422
Study First Received: December 14, 2011
Last Updated: May 18, 2015
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:
Metachromatic Leukodystrophy (MLD)
Recombinant human arylsulfatase A (rhASA)
Intrathecal Drug Delivery Device (IDDD)

Additional relevant MeSH terms:
Leukodystrophy, Metachromatic
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Demyelinating Diseases
Genetic Diseases, Inborn
Hereditary Central Nervous System Demyelinating Diseases
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Sulfatidosis processed this record on August 27, 2015