Open-Label Extension Study Evaluating Safety and Efficacy of HGT-1110 in Patients With Metachromatic Leukodystrophy

This study is enrolling participants by invitation only.
ICON plc
Information provided by (Responsible Party):
Shire Identifier:
First received: June 20, 2013
Last updated: July 6, 2015
Last verified: July 2015

The purpose of this study is to collect long-term safety data in patients with metachromatic leukodystrophy (MLD) who are receiving HGT-1110 and have participated in Study HGT-MLD-070 through Week 40.

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: An Open-Label Extension of Study HGT-MLD-070 Evaluating Long Term Safety and Efficacy of Intrathecal Administration of HGT-1110 in Patients 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: Change from Baseline until End of Study (approximately 4.9 years) ] [ Designated as safety issue: Yes ]
    Safety will be assessed by Adverse Events (AE; type and severity), changes in clinical laboratory testing, vital signs, physical examinations, neurological examinations, cerebrospinal fluid (CSF) chemistries and antibodies.

Secondary Outcome Measures:
  • Clinical activity of IT administration of HGT-1110 on gross motor function [ Time Frame: Change from Baseline until End of Study (approximately 4.9 years) ] [ Designated as safety issue: No ]
    Evaluated using Gross Motor Function Measure-88 (GMFM-88)

  • Concentrations of HGT-1110 in CSF after single and repeated dose administration [ Time Frame: Baseline until End of Study (4.3 years) ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: May 2013
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 (10 mg)
HGT-1110 (Recombinant human arylsulfatase A ), 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
Experimental: Cohort 2 (30 mg)
HGT-1110 (Recombinant human arylsulfatase A ), 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
Experimental: Cohort 3 (100 mg)
HGT-1110 (Recombinant human arylsulfatase A ), 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 study is a multicenter open-label study designed to evaluate safety and efficacy outcomes of HGT-1110 administered intrathecally in children with MLD who have participated in the dose escalation study, HGT-MLD-070, through Week 40 and are receiving study drug every other week (EOW). In this study patients will receive HGT-1110 at the same dose as the cohort to which they were previously assigned in Study HGT-MLD-070 (10, 30, or 100 mg).


Ages Eligible for Study:   up to 13 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patient has participated through Week 40 in Study HGT-MLD-070.
  2. Patient must have no safety or medical issues that contraindicate participation.
  3. The patient, patient's parent or legally authorized representative(s) must provide written informed consent and/or assent (if applicable) prior to performing any study related activities.

Exclusion Criteria:

  1. The patient is unable to comply with the protocol (eg, is unable to return for safety evaluations, or is otherwise unlikely to complete the study) as determined by the Investigator.
  2. The patient has any known or suspected hypersensitivity to agents used for sedation or is thought to be at an unacceptably high risk for associated potential complications of airway compromise or other conditions.
  3. The patient is pregnant or breast feeding.
  4. The patient is enrolled in another clinical study that involves clinical investigations or use of any investigational product (drug or drug delivery device) other than those used in HGT-MLD-070 within 6 months prior to study enrollment or at any time during the study.
  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: NCT01887938

The Children's Hospital at Westmead
Westmead, Australia, 2145
Hospital de Clinicas de Porto Alegre
Porto Alegre, Brazil, 90035-003
Czech Republic
Detska Interni Klinika, Lf Mu A Fn Brno
Brno, Czech Republic, 61300
Copenhagen, Denmark, 2100
Hôpital de Bicêtre
Le Kremlin Bicetre, Ile-de-France, France, 94275
Hopital Femme Mere Enfant
Bron Cedex, France, 69 677
CHU de Nantes
Nantes Cedex 1, France, 44093
Center for Pediatric Clinical Studies (CPCS)
Tubingen, Baden-Wuerttemberg, Germany, 72076
Osaka University Hospital
Osaka, Japan, 565-0871
Sponsors and Collaborators
ICON plc
Study Director: Anna Wijatyk, MD Shire
  More Information

No publications provided

Responsible Party: Shire Identifier: NCT01887938     History of Changes
Other Study ID Numbers: HGT-MLD-071, UTN: U1111-1153-1480, 2012-003775-20
Study First Received: June 20, 2013
Last Updated: July 6, 2015
Health Authority: Denmark: Danish Health and Medicines Authority
Germany: Federal Institute for Drugs and Medical Devices
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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 July 30, 2015