Extension of HGT-HIT-045 Evaluating Long-Term Safety and Clinical Outcomes of Idursulfase (IT)in Conjunction With Elaprase in Pediatric Patients With Hunter Syndrome and Cognitive Impairment

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01506141
First received: December 15, 2011
Last updated: June 9, 2014
Last verified: March 2014
  Purpose

Elaprase, a large molecular protein, is not expected to cross the blood brain barrier when administered intravenously. A revised formulation of idursulfase, idursulfase-IT, that differs from that of the intravenous (IV) formulation, Elaprase, has been developed to be suitable for delivery into the cerebrospinal fluid (CSF) via intrathecal administration.

This extension study of HGT-HIT-045 is designed to collect long-term safety data in pediatric patients with Hunter syndrome and cognitive impairment who are receiving intrathecal idursulfase-IT and intravenous Elaprase enzyme replacement therapy.


Condition Intervention Phase
Hunter Syndrome
Drug: Idursulfase-IT
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Extension of Study HGT-HIT-045 Evaluating Long-Term Safety and Clinical Outcomes of Intrathecal Idursulfase-IT Administered in Conjunction With Intravenous Elaprase® in Pediatric Patients With Hunter Syndrome and Cognitive Impairment

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Safety of intrathecal idursulfase-IT administration [ Time Frame: 30 Months ] [ Designated as safety issue: No ]
    Safety of intrathecal administration of idursulfase-IT will be measured by type and severity of adverse events (AEs), changes in clinical laboratory testing (serum chemistry including liver function tests, hematology, urinalysis), 12-lead ECG, CSF chemistries, and anti-idursulfase antibodies (in CSF and serum by isotype: immunoglobulin (Ig) IgG, IgA, IgM, IgE and antibodies having enzyme neutralizing activity.


Secondary Outcome Measures:
  • Pharmacokinetic (PK) parameters of idursulfase-IT administered in conjunction with Elaprase in CSF and blood. [ Time Frame: PK in blood at time 0, 1, 2, 3, 4, 6, 8, 12, 24 30 and 36 hours every 12 months upon initiation of study, CSF at time immediately prior to each monthly dose out to 30 months. ] [ Designated as safety issue: No ]
    Single and multiple-dose PK profiles for idursulfase following IT and IV infusions will be established by analyzing standard PK parameters including: area under the curve (AUC), maximum serum concentration (Cmax), time to maximum serum concentration (Tmax), serum clearance normalized for body weight (CL), apparent volume of distribution at steady-state (Vss), Vss normalized for body weight (Vss %BW), mean residence time (MRT) and elimination half life (t1/2).

  • Change from baseline in CSF biomarkers. [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Change from baseline and percent change from baseline in CSF biomarker (glycosaminoglycans (GAGs), GAG-degradation products, sulfated HS/DS oligosaccharides) values.

  • Change from baseline in urinary GAGs and GAG-degradation products [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Change from baseline and percent change from baseline in observed urinary GAG biomarker values.


Estimated Enrollment: 20
Study Start Date: August 2010
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Idursulfase-IT
Idursulfase-IT administered once monthly at the dose used in study HGT-HIT-045 via intrathecal drug delivery device (IDDD)
Drug: Idursulfase-IT
Idursulfase-IT administered once monthly at the dose used in study HGT-HIT-045 via intrathecal drug delivery device (IDDD)

  Eligibility

Ages Eligible for Study:   3 Years to 18 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient must have completed all study requirements and end of study assessments for study HGT-HIT-045 prior to enrolling in Study HGT-HIT-046 and must have no safety or medical issues that contraindicate participation.
  • The patient's parent(s) or legally authorized guardian(s) must have voluntarily signed an Institutional Review Board (IRB)/Independent Ethics Committee(IEC)-approved informed consent form after all relevant aspects of the study have been explained and discussed. Consent of the patient's parent(s) or legally authorized guardian(s) and the patient's assent, as relevant, must be obtained.
  • That patient has received and tolerated a minimum of 12 months of treatment with weekly IV infusions of Elaprase and has received 80% of the total planned infusions within the last 6 months.

Exclusion Criteria:

  • Patient has received treatment with any investigational drug (other than idursulfase-IT) or device within 30 days prior to study entry.
  • 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.
  • Patient has experienced an adverse reaction to study drug in Study HGT-HIT-045 that contraindicates further treatment with intrathecal idursulfase-IT.
  • Patient has a known hypersensitivity to any of the components of idursulfase-IT.
  • For patients who were previously untreated with intrathecal idursulfase-IT in Study HGT-HIT-045, the patient has an opening CSF pressure upon lumbar puncture that exceeds 30.0 cm H2O
  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 ClinicalTrials.gov identifier: NCT01506141

Locations
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
United States, Oregon
Legacy Emanuel Hospital
Portland, Oregon, United States, 97227
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84312
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
United Kingdom
Birmingham Children's Hospital
Birmingham, United Kingdom, B46NH
Sponsors and Collaborators
Shire
Investigators
Principal Investigator: Joseph Muenzer, MD, PhD University of North Carolina, Chapel Hill
  More Information

Publications:
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01506141     History of Changes
Other Study ID Numbers: HGT-HIT-046, 2011-000212-25
Study First Received: December 15, 2011
Last Updated: June 9, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Shire:
hunters syndrome
hunter's syndrome
hunter disease
hunters disease
hunter's disease
MPS II
MPSII
MPS2
MPS 2
mps 2
mps ii
mucopolysaccharides
lysosomal storage disease
lysosomal storage disorder
chronic ear infection
enlarged adenoids
mps symptoms
mps diagnosis
ert treatment
elaprase
idursulfase
iduronate sulfatase
iduronate 2 sulfatase
enzyme replacement therapy
hunter syndrome treatment
hunter's syndrome treatment
hunter syndrome therapy
hunter's disease treatment
mps society

Additional relevant MeSH terms:
Mucopolysaccharidosis II
Cognition Disorders
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Mucopolysaccharidoses
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on August 01, 2014