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Study of Long Term Safety and Clinical Outcomes of Idursulfase IT and Elaprase Treatment in Pediatric Participants Who Have Completed Study HGT-HIT-094

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ClinicalTrials.gov Identifier: NCT02412787
Recruitment Status : Enrolling by invitation
First Posted : April 9, 2015
Last Update Posted : October 16, 2018
Sponsor:
Information provided by (Responsible Party):
Shire

Brief Summary:
This extension study will allow participants that completed Study HGT-HIT-094 to continue receiving Elaprase treatment in conjunction with idursulfase IT or to continue receiving Elaprase treatment and begin concurrent IT treatment for those that did not received idursulfase IT treatment in Study HGT-HIT-094.

Condition or disease Intervention/treatment Phase
Hunter Syndrome Drug: Idursulfase-IT Drug: Elaprase Phase 2 Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 49 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Extension of Study HGT-HIT-094 Evaluating Long Term Safety and Clinical Outcomes of Intrathecal Idursulfase Administered in Conjunction With Elaprase® in Patients With Hunter Syndrome and Cognitive Impairment
Actual Study Start Date : April 1, 2015
Estimated Primary Completion Date : September 1, 2022
Estimated Study Completion Date : September 1, 2022


Arm Intervention/treatment
Experimental: Idursulfase-IT
Participants will receive 10 milligrams (mg) of idursulfase-IT intrathecally via intrathecal drug delivery device (IDDD) or lumbar puncture (LP) once every 28 days along with standard-of-care therapy with Elaprase for 240 weeks. Participants who are younger than 3 years of age will receive an adjusted dose of 7.5 mg (greater than [>] 8 months to 30 months of age) and 10 mg (>30 months to 3 years of age) of idursulfase-IT.
Drug: Idursulfase-IT
Participants will receive 10 mg of idursulfase-IT intrathecally via IDDD or LP once every 28 days. Participants who are younger than 3 years of age will receive an adjusted dose of 7.5 mg (>8 months to 30 months of age) and 10 mg (>30 months to 3 years of age).
Other Name: HGT-2310

Drug: Elaprase
Participants will receive intravenous (IV) Elaprase infusions at a minimum of 48 hours after IT administration of idursulfase-IT.




Primary Outcome Measures :
  1. Number of Participants With Adverse Events [ Time Frame: From start of study drug administration up to 61 months ]
    An adverse event is any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered investigational product-related.

  2. Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters, and 12-lead Electrocardiogram (ECG) Findings [ Time Frame: From start of study drug administration up to 61 months ]
    Number of participants with clinically significant changes will be reported.

  3. Maximum Observed Serum Concentration (Cmax) of Idursulfase in Cerebrospinal Fluid (CSF) [ Time Frame: Baseline through Month 61 ]
    The Cmax of Idursulfase will be assessed.

  4. Change From Baseline in the Concentration of Glycosaminoglycan (GAG) in Cerebrospinal Fluid (CSF) [ Time Frame: Baseline through Month 61 ]
    Concentration of GAG in CSF will be assessed.

  5. Number of Participants who Report Anti-idursulfase Antibodies in Cerebrospinal Fluid (CSF) [ Time Frame: From start of study drug administration up to 61 months ]
    The presence of idursulfase-specific antibodies will be assessed.

  6. Number of Participants who Report Anti-idursulfase Antibodies in Serum [ Time Frame: From start of study drug administration up to 61 months ]
    The presence of idursulfase-specific antibodies will be assessed.


Secondary Outcome Measures :
  1. Change From Baseline in Standard Scores in Cluster Areas of the Differential Ability Scales, Second Edition (DAS-II) [ Time Frame: Baseline through Month 61 ]
    The DAS-II will be used to assess all participants of age 2 years, 6 months or older. The DAS-II comprises 2 overlapping batteries. The Early Years battery is designed for children ages 2 years, 6 months, through 6 years, 11 months. The School Age Battery is designed for children ages 7 years, 0 months through 17 years, 11 months. These batteries are fully co-normed for ages 5 years, 0 months, through 8 years, 11 months. The cluster areas include general conceptual ability (GCA), Verbal, Nonverbal, Spatial, and Special Nonverbal Composite (SNC). The cluster area score represents a score (mean = 100 and standard deviation of 15) on which higher scores indicate a higher level of cognitive ability.

  2. Change From Baseline in Age Equivalent Scores of the Bayley Scales of Infant Development, Third Edition (BSID-III) Domains [ Time Frame: Baseline through Month 61 ]
    Participants who are younger than 2 years, 6 months, will be assessed using the BSID-III. The BSID--III is a series of measurements to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers and consists of a series of developmental play tasks. Raw scores (range 40-160) will be converted to age- equivalent scores to measure ability, skill, and knowledge, expressed as the age at which most individuals reach the same level (age norm; range: 0, unbound ).

  3. Change From Baseline in Development Quotient (DQ) of the Bayley Scales of Infant Development, Third Edition (BSID-III) Domains [ Time Frame: Baseline through Month 61 ]
    Participants who are younger than 2 years, 6 months, will be assessed using the BSID-III. The BSID--III is a series of measurements to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers and consists of a series of developmental play tasks. The development quotient (DQ) is a means to express a neurodevelopmental/cognitive delay which will be computed as a ratio and expressed as a percentage using the age equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range: 0-100).

  4. Change From Baseline in Standard Scores of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Domains [ Time Frame: Baseline through Month 61 ]
    The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following 5 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other 4 domains). The standard scores represent a score (mean = 100 and standard deviation of 15) on which higher scores indicate a higher level of cognitive ability.

  5. Change From Baseline in Age Equivalents of the Differential Ability Scales, Second Edition (DAS-II) [ Time Frame: Baseline through Month 61 ]
    The DAS-II will be used to assess all participants of age 2 years, 6 months or older. The DAS-II comprises 2 overlapping batteries. The Early Years battery is designed for children ages 2 years, 6 months, through 6 years, 11 months. The School Age Battery is designed for children ages 7 years, 0 months through 17 years, 11 months. These batteries are fully co-normed for ages 5 years, 0 months, through 8 years, 11 months. The subtests include Verbal Comprehension, Picture Similarities, Naming Vocabulary, Pattern Construction, Matrices, and Copying for the DAS-II Early Years and Recall of Designs, Word Definitions, Pattern Construction, Matrices, Verbal Similarities, and Sequential and Quantitative Reasoning for the DAS-II School Years. The subtest score represents a score (mean = 50 and standard deviation of 10) on which higher scores indicate a higher level of cognitive ability.

  6. Change From Baseline in Developmental Quotients (DQ) of the Differential Ability Scales, Second Edition (DAS-II) [ Time Frame: Baseline through Month 61 ]
    The DAS-II will be used to assess all participants of age 2 years, 6 months or older. The DAS-II comprises 2 overlapping batteries. The Early Years battery is designed for children ages 2 years, 6 months, through 6 years, 11 months. The School Age Battery is designed for children ages 7 years, 0 months through 17 years, 11 months. These batteries are fully co-normed for ages 5 years, 0 months, through 8 years, 11 months. The subtests include Verbal Comprehension, Picture Similarities, Naming Vocabulary, Pattern Construction, Matrices, and Copying for the DAS-II Early Years and Recall of Designs, Word Definitions, Pattern Construction, Matrices, Verbal Similarities, and Sequential and Quantitative Reasoning for the DAS-II School Years. The DQ will be computed as a ratio and expressed as a percentage using the age-equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range, 0-100).

  7. Change From Baseline in T-scores of the Differential Ability Scales, Second Edition (DAS-II) [ Time Frame: Baseline through Month 61 ]
    The DAS-II will be used to assess all participants of age 2 years, 6 months or older. The DAS-II comprises 2 overlapping batteries. The Early Years battery is designed for children ages 2 years, 6 months, through 6 years, 11 months. The School Age Battery is designed for children ages 7 years, 0 months through 17 years, 11 months. These batteries are fully co-normed for ages 5 years, 0 months, through 8 years, 11 months. The subtests include Verbal Comprehension, Picture Similarities, Naming Vocabulary, Pattern Construction, Matrices, and Copying for the DAS-II Early Years and Recall of Designs, Word Definitions, Pattern Construction, Matrices, Verbal Similarities, and Sequential and Quantitative Reasoning for the DAS-II School Years. The subtest score represent a score (mean = 50 and standard deviation of 10) on which higher scores indicate a higher level of cognitive ability.

  8. Change From Baseline in Age Equivalents of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Sub Domains [ Time Frame: Baseline through Month 61 ]
    The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following subdomains of 5 key domains: Communication (Receptive, Expressive, Written), Daily Living Skills (Personal, Domestic, Community), Socialization (Interpersonal Relationships, Play and Leisure Time, Coping Skills), Motor Skills (Gross, Fine). The mean age equivalent score will be obtained by averaging out the age-equivalent scores for the all the sub-domains except for Gross and Fine motor skills (range: 0, unbound).

  9. Change From Baseline in Developmental Quotients (DQ) of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Sub Domains [ Time Frame: Baseline through Month 61 ]
    The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following subdomains of 5 key domains: Communication (Receptive, Expressive, Written), Daily Living Skills (Personal, Domestic, Community), Socialization (Interpersonal Relationships, Play and Leisure Time, Coping Skills), Motor Skills (Gross, Fine). The DQ will be computed as a ratio and expressed as a percentage using the age-equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range, 0-100).

  10. Change From Baseline in T-scores of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Sub Domains [ Time Frame: Baseline through Month 61 ]
    The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following subdomains of 5 key domains: Communication (Receptive, Expressive, Written), Daily Living Skills (Personal, Domestic, Community), Socialization (Interpersonal Relationships, Play and Leisure Time, Coping Skills), Motor Skills (Gross, Fine). The subtest score represent a score (mean = 50 and standard deviation of 10) on which higher scores indicate a higher level of cognitive ability.

  11. Change From Baseline in V-scale Scores of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Maladaptive Behavior Index and its Subscales [ Time Frame: Baseline through Month 61 ]
    The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. Maladaptive behavior index is a composite of the internalizing, externalizing, and other types of undesirable behavior that may interfere with the individual's adaptive functioning. The V-scale scores represent a score (mean = 15 and standard deviation of 3; range: 1-24) on which higher scores indicate a higher level of adaptive functioning.

  12. Change From Baseline in Observed Maladaptive Levels of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Maladaptive Behavior Index and its Subscales [ Time Frame: Baseline through Month 61 ]
    The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. Maladaptive behavior index is a composite of the internalizing, externalizing, and other types of undesirable behavior that may interfere with the individual's adaptive functioning.

  13. Change From Baseline in Brain Structure Volume as Measured by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline through Month 61 ]
    Brain structure volume will be assessed from brain total intracranial volume, brain total tissue volume, brain total white matter, brain total gray matter, and total CSF volume as measured by MRI.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must have completed Visit Week 52 assessments in Study HGT-HIT-094 (NCT02055118).
  • The participant'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 participant's parent(s) or legally authorized guardian(s) and the participant's assent, as relevant, must be obtained.
  • The participant has continued to receive Elaprase on a regular basis in Study HGT-HIT-094 (NCT02055118).

Exclusion Criteria:

  • The participant has experienced, in the opinion of the Investigator, a safety or medical issue that contraindicates treatment with idursulfase-IT, including, but not limited to, uncontrolled seizure disorder, bleeding disorder, and clinically relevant hypertension.
  • The participant has a known hypersensitivity to any of the components of idursulfase-IT.
  • The participant has clinically relevant intracranial hypertension.
  • The participant is enrolled in another clinical study, other than HGT-HIT-094 (NCT02055118), that involves clinical investigations or use of any investigational product (drug or [intrathecal/spinal] device) within 30 days prior to study enrollment or at any time during the study.
  • The participant has any known or suspected hypersensitivity to anesthesia or is thought to be at an unacceptably high risk for anesthesia due to compromised airways or other conditions.
  • The participant has a condition that is contraindicated as described in the SOPH-A-PORT® Mini S, Implantable Access Port, Spinal, Mini Unattached, with Guidewire (SOPH-A-PORT Mini S) intrathecal drug delivery device (IDDD) Instructions for Use, including:

    1. The participant has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT Mini S device.
    2. The participant's body size is too small to support the size of the SOPH-A-PORT Mini S Access Port, as judged by the Investigator.
    3. The participant's drug therapy requires substances known to be incompatible with the materials of construction.
    4. The participant has a known or suspected local or general infection.
    5. The participant is at risk of abnormal bleeding due to a medical condition or therapy.
    6. The participant has one or more spinal abnormalities that could complicate safe implantation or fixation.
    7. The participant has a functioning CSF shunt device.
    8. The participant has shown an intolerance to an implanted device.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02412787


Locations
United States, California
Children's Hospital and Research Center at Oakland
Oakland, California, United States, 94609
United States, Illinois
Ann & Robert H Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27514
Australia
Women's and Children's Hospital
Adelaide, Australia, 5006
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
France
Hôpital Femme Mère Enfants
Bron, France, 69677
Mexico
Instituto Nacional de Pediatría
Coyoacan, Ciudad De México, Mexico, 04530
Spain
Hospital Infantil Universitario Niño Jesus
Madrid, Spain, 28009
United Kingdom
Royal Manchester Children's Hospital
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Shire
Investigators
Study Director: Study Director Shire

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT02412787     History of Changes
Other Study ID Numbers: SHP609-302
2014-004143-13 ( EudraCT Number )
First Posted: April 9, 2015    Key Record Dates
Last Update Posted: October 16, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Syndrome
Mucopolysaccharidosis II
Disease
Pathologic Processes
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