COVID-19 studies are our top priority.

For new and updated trial submissions, we are processing trials as quickly as possible and appreciate your patience. We recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02055118




Registration number
NCT02055118
Ethics application status
Date submitted
17/01/2014
Date registered
4/02/2014
Date last updated
11/06/2021

Titles & IDs
Public title
Study of Intrathecal Idursulfase-IT Administered in Conjunction With Elaprase® in Pediatric Patients With Hunter Syndrome and Early Cognitive Impairment
Scientific title
A Controlled, Randomized, Two-arm, Open-label, Assessor-blinded, Multicenter Study of Intrathecal Idursulfase-IT Administered in Conjunction With Elaprase® in Pediatric Patients With Hunter Syndrome and Early Cognitive Impairment
Secondary ID [1] 0 0
2013-002885-38
Secondary ID [2] 0 0
HGT-HIT-094
Universal Trial Number (UTN)
Trial acronym
AIM-IT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hunter Syndrome 0 0
Condition category
Condition code
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above
Mental Health 0 0 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - idursulfase-IT
Other interventions - No IT treatment

Experimental: idursulfase-IT - 10 mg administered via IT using IDDD (intrathecal drug delivery device) once a month for 52 weeks.

Other: Nontreatment control - Patients will receive weekly standard of care treatment with IV Elaprase only.


Other interventions: idursulfase-IT
10mg

Other interventions: No IT treatment
Standard of Care

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in the Differential Ability Scales, Second Edition (DAS-II) General Conceptual Ability (GCA) Standard Score at Week 52 - The DAS-II was used to assess cognitive development in all randomized participants. The GCA standard score of the DAS-II was used to obtain a general measure of cognitive ability. The GCA score represent a score (mean = 100 and standard deviation of 15) on which higher scores indicate a higher level of cognitive ability. The score ranges from 30 to 170. A positive change value indicates improvement in cognitive ability.
Timepoint [1] 0 0
Baseline, Week 52
Secondary outcome [1] 0 0
Change From Baseline in the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Adaptive Behavior Composite (ABC) Score at Week 52 - 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 4 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other 4 domains). The ABC score ranges from 20 to 160 on which higher scores indicate a higher level of adaptive functioning. A positive change value indicates improvement in adaptive functioning.
Timepoint [1] 0 0
Baseline, Week 52
Secondary outcome [2] 0 0
Change From Baseline in the Differential Ability Scales, Second Edition (DAS-II) General Conceptual Ability (GCA) Standard Score at Weeks 16, 28 and 40 - The DAS-II was used to assess cognitive development in all randomized participants. The GCA standard score of the DAS-II was used to obtain a general measure of cognitive ability. The GCA score represent a score (mean = 100 and standard deviation of 15) on which higher scores indicate a higher level of cognitive ability. The score ranges from 30 to 170. A positive change value indicates improvement in cognitive ability.
Timepoint [2] 0 0
Baseline, Week 16, Week 28 and Week 40
Secondary outcome [3] 0 0
Change From Baseline in the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Adaptive Behavior Composite (ABC) Score at Week 16, 28 and 40 - 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 4 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other 4 domains). The ABC score ranges from 20 to 160 on which higher scores indicate a higher level of adaptive functioning. A positive change value indicates improvement in adaptive functioning.
Timepoint [3] 0 0
Baseline, Week 16, Week 28 and Week 40
Secondary outcome [4] 0 0
Change From Baseline in Differential Ability Scales, Second Edition (DAS-II) Cluster Standard Scores at Weeks 16, 28, 40 and 52 - The DAS-II was used to assess cognitive development in all randomized participants. The cluster scores represent a score (mean = 100 and standard deviation of 15) on which higher scores indicate a higher level of cognitive ability in each cluster: verbal (score range: 31-169), nonverbal (score range: 31-166) and spatial (score range: 32-170).
Timepoint [4] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [5] 0 0
Change From Baseline in Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Standard Scores of Other Domains at Weeks 16, 28, 40, 52 - 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 4 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. A positive change value indicates improvement in adaptive functioning. Communication, daily living skills, socialization and motor skills domains were reported here. The range for individual standard scores is 20-160.
Timepoint [5] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [6] 0 0
Change From Baseline of Age Equivalent Score for Early Years of Core Subtests of the Differential Ability Scales, Second Edition (DAS-II) at Weeks 16, 28, 40 and 52 - The DAS-II was used to assess cognitive development in all randomized participants. The early years battery is designed for children ages 2 years 6 months through 6 years 11 months. Standardized scores were converted to age equivalent scores to measure ability, skill, and knowledge expressed as the age at which most individuals reach the same level. The mean age equivalent score is obtained by averaging out the age-equivalent scores. The higher score indicates greater cognitive ability. The subtest score represent a score (mean = 50 and standard deviation of 10) on which higher scores indicate a higher level of cognitive ability. A positive change value indicates improvement in cognitive ability.
Timepoint [6] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [7] 0 0
Change From Baseline of Age Equivalents for School Age of Core Subtests of the Differential Ability Scales, Second Edition (DAS-II) at Weeks 16, 28, 40 and 52 - The DAS-II was used to assess cognitive development in all randomized participants. The school age battery is designed for children ages 7 years 0 months through 17 years 11 months. Standardized scores were converted to age equivalent scores to measure ability, skill, and knowledge expressed as the age at which most individuals reach the same level. The mean age equivalent score is obtained by averaging out the age-equivalent scores. The higher score indicates greater cognitive ability. The subtest score represents a score (mean = 50 and standard deviation of 10) on which higher scores indicate a higher level of cognitive ability. A positive change value indicates improvement in cognitive ability. In the below table, SQR stands for "Sequential & Quantitative Reasoning".
Timepoint [7] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [8] 0 0
Change From Baseline of Development Quotients for Early Years of Core Subtests of the Differential Ability Scales, Second Edition (DAS-II) at Weeks 16, 28, 40 and 52 - The DAS-II was used to assess cognitive development in all randomized participants. The early years battery is designed for children ages 2 years 6 months through 6 years 11 months. The DQ is a means to express a neurodevelopmental/cognitive delay. The DQ was 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). The higher score indicates greater cognitive ability. The subtest score represent a score (mean = 50 and standard deviation of 10) on which higher scores indicate a higher level of cognitive ability. A positive change value indicates improvement in cognitive ability.
Timepoint [8] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [9] 0 0
Change From Baseline of Development Quotients for School Age of Core Subtests of the Differential Ability Scales, Second Edition (DAS-II) at Weeks 16, 28, 40 and 52 - The DAS-II was used to assess cognitive development in all randomized participants. The school age battery is designed for children ages 7 years 0 months through 17 years 11 months. The DQ is a means to express a neurodevelopmental/cognitive delay. The DQ was 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). The higher score indicates greater cognitive ability. The subtest score represent a score (mean = 50 and standard deviation of 10) on which higher scores indicate a higher level of cognitive ability. A positive change value indicates improvement in cognitive ability. In the below table, SQR stands for "Sequential & Quantitative Reasoning".
Timepoint [9] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [10] 0 0
Change From Baseline of T-scores for Early Years of Core Subtests of the Differential Ability Scale, Second Edition (DAS-II) at Weeks 16, 28, 40 and 52 - The DAS-II was used to assess cognitive development in all randomized participants. The early years battery is designed for children ages 2 years 6 months through 6 years 11 months. The higher score indicates greater cognitive ability. The subtest score represent a score (mean = 50 and standard deviation of 10) on which higher scores indicate a higher level of cognitive ability. A positive change value indicates improvement in cognitive ability.
Timepoint [10] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [11] 0 0
Change From Baseline of T-scores for School Age of Core Subtests of the Differential Ability Scale, Second Edition (DAS-II) at Weeks 16, 28, 40 and 52 - The DAS-II was used to assess cognitive development in all randomized participants. The school age battery is designed for children ages 7 years 0 months through 17 years 11 months. The higher score indicates greater cognitive ability. The subtest score represent a score (mean = 50 and standard deviation of 10) on which higher scores indicate a higher level of cognitive ability. A positive change value indicates improvement in cognitive ability. In the below table, SQR stands for "Sequential & Quantitative Reasoning".
Timepoint [11] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [12] 0 0
Change From Baseline of Age Equivalents Scores of Sub-domains of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Weeks 16, 28, 40 and 52 - The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. Standardized scores (range 40-160) were converted to age equivalent scores to measure ability, skill, and knowledge expressed as the age at which most individuals reach the same level. The mean age equivalent score is obtained by averaging out the age-equivalent scores for the all the sub-domains except for Gross and Fine motor skills (range: 0, unbound). A positive value indicates improvement in health and cognition.
Timepoint [12] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [13] 0 0
Change From Baseline of Development Quotients of Sub-domains of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Weeks 16, 28, 40 and 52 - The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. The DQ is a means to express a neurodevelopmental/cognitive delay. The DQ was 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). The overall DQ score is calculated from the mean age-equivalent score obtained by averaging out the age equivalent scores for the all the sub-domains except for Gross and Fine motor skills. This test measures the following 4 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other 4 domains). A positive value indicates improvement in health and cognition.
Timepoint [13] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [14] 0 0
Change From Baseline of V-Scale Scores of Sub-domains of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Weeks 16, 28, 40 and 52 - 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 4 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other 4 domains). 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. A positive change value indicates improvement in adaptive functioning.
Timepoint [14] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [15] 0 0
Change From Baseline of V-Scale Scores of Maladaptive Behavior Index and Its Sub-scales at Weeks 16, 28, 40 and 52 - 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 greater maladaptive behaviors. A positive change value indicates increase of maladaptive behavior.
Timepoint [15] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [16] 0 0
Observed Maladaptive Levels of Maladaptive Behavior Index and Its Sub-scales of Vineland Adaptive Behavior Scales, Second Edition (VABS-II) - 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 (MBI) 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 greater maladaptive behaviors. The v-scale score ranges for MBI, externalizing and internalizing scores are defined as clinically significant: 21-24, elevated: 18-20, average: 1-17.
Timepoint [16] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [17] 0 0
Maximum Observed Drug Concentration (Cmax) of Idursulfase After IT Administration - The Cmax of idursulfase after IT administration was reported.
Timepoint [17] 0 0
Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48
Secondary outcome [18] 0 0
Time to Reach Maximum Drug Concentration (Tmax) of Idursulfase After IT Administration - The tmax of idursulfase after IT administration was reported.
Timepoint [18] 0 0
Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48
Secondary outcome [19] 0 0
Area Under the Concentration Versus Time Curve From Zero From the Time of Dosing to the Last Measurable Concentration (AUC0-t) of Idursulfase After IT Administration - The AUC0-t of idursulfase after IT administration was reported.
Timepoint [19] 0 0
Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48
Secondary outcome [20] 0 0
Terminal Half-life (t1/2) of Idursulfase After IT Administration - The t1/2 of idursulfase after IT administration was reported.
Timepoint [20] 0 0
Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48
Secondary outcome [21] 0 0
Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed (CL/F) of Idursulfase After IT Administration - The CL/F of idursulfase after IT administration was reported.
Timepoint [21] 0 0
Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48
Secondary outcome [22] 0 0
Change From Baseline in the Concentration of Glycosaminoglycans (GAG) in Cerebrospinal Fluid (CSF) at Week 52 - Change from baseline in the concentration of GAG in CSF was reported.
Timepoint [22] 0 0
Baseline, Week 52
Secondary outcome [23] 0 0
Concentration of Idursulfase in Cerebrospinal Fluid (CSF) - CSF samples were collected via the IDDD or lumbar puncture prior to the injection of Idursulfase-IT.
Timepoint [23] 0 0
Pre-dose on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [24] 0 0
Participant Response to Quality of Life EuroQol-5D (EQ-5D) Questionnaire at Week 52 - The EQ-5D provides a descriptive profile and index value for health status. The questionnaire measures 5 dimensions of health status: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. For each dimension, there are 5 levels of response: no problems, slight problems, moderate problems, severe problems, and unable to do/extreme problems.
Timepoint [24] 0 0
Week 52
Secondary outcome [25] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Intrathecal Drug Delivery Device (IDDD)-Related Adverse Events - An adverse event (AE) was 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. Treatment-emergent AEs for the no IT treatment group were defined as all AEs occurring on or after the date of randomization and at or before the end of the study (EOS) visit. Treatment-emergent AEs for the IT treatment group were defined as all AEs occurring on or after the date of the first IDDD implant surgery or Treatment-Emergentfirst dose of the investigational product (whichever was earlier) and at or before the EOS visit (+30 days) or 2 weeks after the removal of the last IDDD (whichever was later).
Timepoint [25] 0 0
From start of study treatment up to Week 53
Secondary outcome [26] 0 0
Composite Scores of Bayley Scales of Infant Development (BSID-III) Scale in Substudy Population - Participants who were younger than 3 years were 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 composite score for the cognitive scale, language scale, and motor scale are normed and have a mean=100, SD=15 and range of 40-160. Higher values denote stronger skills and abilities in the domain, indicating better outcomes. Participant wise data at evaluable timepoints was reported for this outcome.
Timepoint [26] 0 0
Baseline up to Week 52
Secondary outcome [27] 0 0
Percentile Scores of Bayley Scales of Infant Development (BSID-III) Scale in Substudy Population - Participants who were younger than 3 years were 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. Percentile scores range from 1 to 99 with 50 as the mean and median. Higher percentile means higher the rank of the child relative to the normed population. Participant wise data at evaluable timepoints was reported for this outcome.
Timepoint [27] 0 0
Baseline up to Week 52
Secondary outcome [28] 0 0
Age Equivalent Scores of Bayley Scales of Infant Development (BSID-III) Scale in Substudy Population - Participants who were younger than 3 years were 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. Standardized scores (range 40-160) were 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). Higher values present better outcomes. Participant wise data at evaluable timepoints was reported for this outcome.
Timepoint [28] 0 0
Baseline up to Week 52
Secondary outcome [29] 0 0
Chronological Age of Bayley Scales of Infant Development (BSID-III) Scale in Substudy Population - Participants who were younger than 3 years were 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. Chronological age of the participants when assessed by the BSID-III scale was reported. Range 16.59 - 45.21 months. Participant wise data at evaluable timepoints was reported for this outcome.
Timepoint [29] 0 0
Baseline up to Week 52
Secondary outcome [30] 0 0
Development Quotient (DQ) of Bayley Scales of Infant Development (BSID-III) Scale in Substudy Population - Participants who were younger than 3 years were 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). Higher values present better outcomes. Participant wise data at evaluable timepoints was reported for this outcome.
Timepoint [30] 0 0
Baseline up to Week 52
Secondary outcome [31] 0 0
Raw Scores of Bayley Scales of Infant Development (BSID-III) Scale in Substudy Population - Participants who were younger than 3 years were 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 are converted to scaled scores that are based on normed populations. Raw score ranges: Cognitive scale 0-91, Receptive communication 0-49, Expressive communication 0-48, Fine motor 0-66 and Gross motor 0-72. Higher values indicate better outcomes. Participant wise data at evaluable timepoints was reported for this outcome.
Timepoint [31] 0 0
Baseline up to Week 52

Eligibility
Key inclusion criteria
Inclusion Criteria Inclusion Criteria for the Pivotal Study

Patients must meet all of the following criteria to be considered eligible for
randomization in the pivotal study:

1. The patient is male and is =3 and <18 years of age at the time of informed consent.

(Patients who are younger than 3 years of age may be enrolled in a separate substudy
provided that they meet other inclusion criteria, provided below.)

2. The patient must have a documented diagnosis of MPS II.

3. The patient has evidence at Screening of Hunter syndrome-related cognitive impairment
defined as follows:

A patient who is =3 and <13 years of age must have one of the following criteria (3a
OR 3b):

1. A GCA score =55 and =85 OR

2. If the patient has a GCA score at Screening >85, there must be evidence of a
decrease in GCA score of =10 points over 12 months from a previously documented
test result in observational study HGT-HIT-090.

A patient who is =13 and <18 years of age must have both of the following
criteria (3c AND 3d):

3. A GCA score of =55 and =85. AND

4. There must be evidence of a decrease in GCA score of =10 points over 12 months
from a previously documented

4. The patient has received and tolerated a minimum of 4 months of therapy with Elaprase
during the period immediately prior to Screening.

5. The patient must have sufficient auditory capacity, with a hearing aid(s), if needed,
in the Investigator's judgment to complete the required protocol testing and must be
compliant with wearing the hearing aid(s), if needed, on scheduled testing days.

6. The patient's parent(s) or legally authorized guardian(s) must have voluntarily signed
an Institutional Review Board/Independent Ethics Committee 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, if applicable, must be obtained prior to the start of any study procedures.

Inclusion Criteria for the Substudy

Patients must meet all of the following criteria to be considered eligible for enrollment
in the separate substudy:

1. The patient is male and is <3 years of age at the time of informed consent.

2. The patient must have a documented diagnosis of MPS II.

3. The patient has evidence at Screening of Hunter syndrome-related cognitive impairment

4. The patient has received and tolerated a minimum of 4 months of therapy with Elaprase
during the period immediately prior to Screening.

5. The patient must have sufficient auditory capacity, with a hearing aid(s), if needed,
in the Investigator's judgment to complete the required protocol testing and must be
compliant with wearing the hearing aid(s), if needed, on scheduled testing days.

6. The patient's parent(s) or legally authorized guardian(s) must have voluntarily signed
an Institutional Review Board/Independent Ethics Committee 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) must be obtained
prior to the start of any study procedures.
Minimum age
No limit
Maximum age
18 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

Patients who meet any of the following criteria are not eligible to be randomized into the
pivotal study or enrolled in the separate substudy:

1. The patient has clinically significant non-Hunter syndrome-related CNS involvement
(such as Fragile-X syndrome) which is judged by the Investigator to be likely to
interfere with the accurate administration and interpretation of protocol assessments.

2. The patient has a large chromosomal deletion or complex rearrangement that includes a
deletion of the FMR1 and/or FMR2 genes.

3. The patient has a significant medical or psychiatric comorbidity(ies) that might
affect study data or confound the integrity of study results.

4. The patient has contra-indications for performance of lumbar puncture such as
musculoskeletal/spinal abnormalities or risk of abnormal bleeding.

5. The patient has a history of complications from previous lumbar punctures or technical
challenges in conducting lumbar punctures such that the potential risks would exceed
possible benefits for the patient.

6. The patient has an opening CSF pressure upon lumbar puncture that exceeds 30.0 cm H2O.

7. The patient has experienced infusion-related anaphylactoid event(s) or has evidence of
consistent severe adverse events related to treatment with Elaprase which, in the
Investigator's opinion, may pose an unnecessary risk to the patient.

8. The patient has received a cord blood or bone marrow transplant at any time or has
received blood product transfusions within 90 days prior to Screening.

9. The patient has a history of poorly controlled seizure disorder.

10. The patient is unable to comply with the protocol (eg, has significant hearing or
vision impairment, a clinically relevant medical condition making implementation of
the protocol difficult, unstable social situation, known clinically significant
psychiatric/behavioral instability, is unable to return for safety evaluations, or is
otherwise unlikely to complete the study), as determined by the Investigator.

11. The patient is enrolled in another clinical study that involves clinical investigation
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.

12. The patient 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.

13. The patient has a condition that is contraindicated as described in the SOPH-A-PORT
Mini S IDDD Instructions for Use (IFU), including but not limited to the presence of a
CSF shunt device in the patient.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Women's and Children's Hospital, 72 King William Road - North Adelaide
Recruitment postcode(s) [1] 0 0
5006 - North Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
France
State/province [5] 0 0
Bron
Country [6] 0 0
Mexico
State/province [6] 0 0
Ciudad De México
Country [7] 0 0
Spain
State/province [7] 0 0
Madrid
Country [8] 0 0
United Kingdom
State/province [8] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Shire
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Study HGT-HIT-094 is a multicenter study designed to determine the effect on clinical
parameters of neurodevelopmental status of monthly IT administration of idursulfase-IT 10 mg
for 12 months in pediatric patients with Hunter syndrome and cognitive impairment who have
previously received and tolerated a minimum of 4 months of therapy with Elaprase.
Trial website
https://clinicaltrials.gov/show/NCT02055118
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Takeda
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications