Hunter syndrome and cognitive impairment MedDRA version: 20.1 Level: PT Classification code 10056889 Term: Mucopolysaccharidosis II System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: LLT Classification code 10056917 Term: Hunter's syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Idursulfase-IT
Product Code: HGT-2310
Pharmaceutical Form: Solution for injection
INN or Proposed INN: IDURSULFASE
CAS Number: 50936-59-9
Current Sponsor code: HGT-2310
Other descriptive
Sponsors
Shire Human Genetic Therapies, Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Subjects must have completed Visit Week 52 assessments in Study HGT-HIT-094 2. The subject’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 subject’s parent(s) or legally authorized guardian(s) and the subject’s consent/assent, as relevant, must be obtained 3. The subject has continued to receive Elaprase on a regular basis in Study HGT-HIT-094 Are the trial subjects under 18? yes Number of subjects for this age range: 56 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. The subject 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 2. The subject has a known hypersensitivity to any of the components of idursulfase-IT 3. The subject has clinically relevant intracranial hypertension 4. The subject is enrolled in another clinical study, other than HGT-HIT-094, 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 5. The subject 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. 6. The subject has a condition that is contraindicated as described in the SOPH-A-PORT Mini S IDDD Instructions for Use, including: a. The subject has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT Mini S device b. The subject’s body size is too small to support the size of the SOPH-A-PORT Mini S Access Port, as judged by the Investigator c. The subject’s drug therapy requires substances known to be incompatible with the materials of construction d. The subject has a known or suspected local or general infection e. The subject is at risk of abnormal bleeding due to a medical condition or therapy f. The subject has one or more spinal abnormalities that could complicate safe implantation or fixation g. The subject has a functioning CSF shunt device h. The subject has shown an intolerance to an implanted device
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate long-term safety in subjects with Hunter syndrome and cognitive impairment who are receiving intrathecal idursulfase-IT and intravenous (IV) Elaprase® enzyme replacement therapy (ERT);Secondary Objective: The secondary objectives of this study are to evaluate long term clinical efficacy outcomes in subjects with Hunter syndrome and cognitive impairment who are treated with idursulfase-IT in conjunction with Elaprase therapy with respect to the following: • Cognitive function as measured by General Conceptual Ability (GCA), the cluster areas and subtests of the Differential Abilities Scale, 2nd edition (DAS-II) or the British Abilities Scales, Second Edition (BAS-II), or domains of the Bayley Scales of Infant Development, Third Edition (BSID-III) • Adaptive behavior as measured by the Adaptive Behavior Composite (ABC) score and standard domain scores of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) • Brain structure volume as measured by magnetic resonance imaging (MRI) For PK/PD, health economics and outcome research and device objectives see protocol section 2.3 - 2.5. ;Primary end point(s): Safety will be assessed during the study by the following: • adverse events (AEs) (by type, severity, and relationship to treatment [idursulfase-IT, the IDDD, device surgical procedure, or IT administration process], IV Elaprase infusion IV Elaprase and/or idursulfase-IT) • changes in clinical laboratory testing (serum chemistry, hematology, urinalysis) • vital signs • 12-lead ECG recordings • CSF laboratory parameters (chemistries, cell counts) • anti-idursulfase antibodies in CSF and serum, including determination of anti-idursulfase antibodies having enzyme neutralizing activity;Timepoint(s) of evaluation of this end point: Adverse events (AEs) will be assessed during all the study. CSF assessments (other than standard chemistry) and clinical laboratory tests of blood and urine will be perf | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: *Initial Treatment Phase: Patients not treated in Study HGT-HIT-094 undergo neurodevelopmental assessment at week 16, 28, 40; EQ-5D-5L at week 4, 16, 28 and 40; Health Resource Utilization and Impact Questionnaire and HS-FOCUS at baseline, week 4, 16, 28 and 40. *Extended Treatment Phase: - Patients not treated in Study HGT-HIT-094 undergo all assessment above at week 52 and thereafter every 24 weeks. - Patients treated in Study HGT-HIT-094 do not undergo neurodevelopmental assessment and EQ-5D-5L at week 52 but thereafter every 24 weeks. Health Resource Utilization and Impact Questionnaire and HS-FOCUS will be performed at week 52 and thereafter every 24 weeks. For all other endpoints please refer to Appendix 1 to 12 of the protocol.;Secondary end point(s): • Change from baseline in DAS-II standard scores: GCA, Special Nonverbal Composite (SNC); and standard cluster scores: Verbal, Nonverbal, Spatial; and/or the age equivalents and Development Quotient (DQ) from the BSID-III domains: Cognitive and Language • Change from baseline in standard composite scores of the VABS-II: ABC and domain standard scores: Communication, Daily Living Skills, Socialization, and Motor Skills • Change from baseline in age equivalents, developmental quotients, and T-scores for the core subtests of the DAS-II: 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 • Change from baseline in age equivalents, developmental quotients, and v-Scale scores of the VABS-II subdomains: Communication (Receptive, Expressive, Written), Daily Living Skills (Personal, Domestic, Community), Socialization (Interpersonal Relationships, Play and Leisure Time, Coping Skills), Motor Skills (Gross, Fine) • Change fr | — |
Countries
Argentina, Australia, Canada, Colombia, France, Mexico, Spain, United Kingdom, United States
Contacts
Public ContactSenior Clinical Project Manager
Shire HGT
Outcome results
None listed