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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-002885-38 | EudraCT Number |
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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.
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.
Mucopolysaccharidosis II (MPS II) is a rare, X-linked, inherited disease that affects males nearly exclusively. The disease is caused by the absence of, or deficiency in, the activity of the lysosomal enzyme, iduronate-2-sulfatase (I2S) which acts to cleave O-linked sulfate moieties from the glycosaminoglycan (GAG) molecules dermatan sulfate and heparan sulfate.
Study HGT-HIT-094 is a controlled, randomized, two-arm, open-label, assessor-blinded, multicenter study 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.
Pediatric patients under 3 years of age will be enrolled into a separate substudy to evaluate the safety and efficacy of idursulfase-IT. The separate substudy is open label and single arm. Patients who are enrolled in the substudy will receive idursulfase-IT treatment and follow the same schedule of study visits.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| idursulfase-IT | Experimental | 10 mg administered via IT using IDDD (intrathecal drug delivery device) once a month for 52 weeks. |
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| Nontreatment control | Other | Patients will receive weekly standard of care treatment with IV Elaprase only. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| idursulfase-IT | Biological | 10mg |
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| No IT treatment |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, Week 52 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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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:
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.)
The patient must have a documented diagnosis of MPS II.
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):
A GCA score ≥55 and ≤85 OR
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):
A GCA score of ≥55 and ≤85. AND
There must be evidence of a decrease in GCA score of ≥10 points over 12 months from a previously documented
The patient has received and tolerated a minimum of 4 months of therapy with Elaprase during the period immediately prior to Screening.
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.
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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital and Research Center at Oakland | Oakland | California | 94609 | United States | ||
| Ann & Robert H Lurie Children's Hospital of Chicago |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37915038 | Derived | Yee KS, Chirila C, Davenport E, Mladsi D, Barnett C, Kronenberger WG. A post hoc analysis of Projected Retained Ability Scores (PRAS) for the longitudinal assessment of cognitive functioning in patients with neuronopathic mucopolysaccharidosis II receiving intrathecal idursulfase-IT. Orphanet J Rare Dis. 2023 Nov 2;18(1):343. doi: 10.1186/s13023-023-02957-2. | |
| 36027721 |
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Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Overall, 103 participants were screened, of them 54 participants failed to meet the randomization and remaining 49 participants were randomized to receive either IT treatment or No IT treatment in pivotal study. A total of 9 participants were enrolled into the substudy.
Study was conducted at 9 centers in Australia, Canada, France, Mexico, Spain, the United Kingdom and the United States between 24 Mar 2014 (first participant first visit) and 28 Sep 2017 (last participant last visit).
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| ID | Title | Description |
|---|---|---|
| FG000 | No IT Treatment | Participants aged 3 to less than (<) 18 years received Elaprase therapy as standard of care for 12 months. |
| FG001 | IT Treatment | Participants aged 3 to < 18 years received intrathecal (IT) injections of 10 milligram (mg) Idursulfase-IT once monthly for 12 months through SOPH-A-PORT Mini S intrathecal drug delivery device (IDDD) along with Elaprase. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol: original | Apr 4, 2013 | Sep 27, 2018 |
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| Other |
Standard of Care |
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| Baseline, Week 52 |
| 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. | Baseline, Week 16, Week 28 and Week 40 |
| 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. | Baseline, Week 16, Week 28 and Week 40 |
| 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). | Baseline, Week 16, Week 28, Week 40 and Week 52 |
| 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. | Baseline, Week 16, Week 28, Week 40 and Week 52 |
| 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. | Baseline, Week 16, Week 28, Week 40 and Week 52 |
| 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". | Baseline, Week 16, Week 28, Week 40 and Week 52 |
| 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. | Baseline, Week 16, Week 28, Week 40 and Week 52 |
| 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". | Baseline, Week 16, Week 28, Week 40 and Week 52 |
| 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. | Baseline, Week 16, Week 28, Week 40 and Week 52 |
| 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". | Baseline, Week 16, Week 28, Week 40 and Week 52 |
| 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. | Baseline, Week 16, Week 28, Week 40 and Week 52 |
| 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. | Baseline, Week 16, Week 28, Week 40 and Week 52 |
| 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. | Baseline, Week 16, Week 28, Week 40 and Week 52 |
| 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. | Baseline, Week 16, Week 28, Week 40 and Week 52 |
| 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. | Baseline, Week 16, Week 28, Week 40 and Week 52 |
| Maximum Observed Drug Concentration (Cmax) of Idursulfase After IT Administration | The Cmax of idursulfase after IT administration was reported. | Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48 |
| Time to Reach Maximum Drug Concentration (Tmax) of Idursulfase After IT Administration | The tmax of idursulfase after IT administration was reported. | Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48 |
| 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. | Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48 |
| Terminal Half-life (t1/2) of Idursulfase After IT Administration | The t1/2 of idursulfase after IT administration was reported. | Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48 |
| 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. | Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48 |
| 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. | Baseline, Week 52 |
| Concentration of Idursulfase in Cerebrospinal Fluid (CSF) | CSF samples were collected via the IDDD or lumbar puncture prior to the injection of Idursulfase-IT. | Pre-dose on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 |
| 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. | Week 52 |
| 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). | From start of study treatment up to Week 53 |
| 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. | Baseline up to Week 52 |
| 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. | Baseline up to Week 52 |
| 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. | Baseline up to Week 52 |
| 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. | Baseline up to Week 52 |
| 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. | Baseline up to Week 52 |
| 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. | Baseline up to Week 52 |
| Chicago |
| Illinois |
| 60611 |
| United States |
| University of North Carolina | Chapel Hill | North Carolina | 27599 | United States |
| Women's and Children's Hospital, 72 King William Road | North Adelaide | 5006 | Australia |
| The Hospital for Sick Children | Toronto | Ontario | M5G 1X8 | Canada |
| Hôpital Femme Mère Enfant | Bron | 69677 | France |
| Instituto Nacional de Pediatría | Coyoacán | Mexico City | 04530 | Mexico |
| Hospital Infantil Universitario Niño Jesus | Madrid | 28009 | Spain |
| Royal Manchester Children's Hospital | Manchester | M13 9WL | United Kingdom |
| Muenzer J, Burton BK, Harmatz P, Gutierrez-Solana LG, Ruiz-Garcia M, Jones SA, Guffon N, Inbar-Feigenberg M, Bratkovic D, Hale M, Wu Y, Yee KS, Whiteman DAH, Alexanderian D; HGT-HIT-094 Study Group. Intrathecal idursulfase-IT in patients with neuronopathic mucopolysaccharidosis II: Results from a phase 2/3 randomized study. Mol Genet Metab. 2022 Sep-Oct;137(1-2):127-139. doi: 10.1016/j.ymgme.2022.07.017. Epub 2022 Aug 2. |
| 35961250 | Derived | Muenzer J, Burton BK, Harmatz P, Gutierrez-Solana LG, Ruiz-Garcia M, Jones SA, Guffon N, Inbar-Feigenberg M, Bratkovic D, Hale M, Wu Y, Yee KS, Whiteman DAH, Alexanderian D; SHP609-302 study group. Long-term open-label extension study of the safety and efficacy of intrathecal idursulfase-IT in patients with neuronopathic mucopolysaccharidosis II. Mol Genet Metab. 2022 Sep-Oct;137(1-2):92-103. doi: 10.1016/j.ymgme.2022.07.016. Epub 2022 Aug 2. |
| FG002 | Substudy | Participants aged less than 3 years received Idursulfase-IT monthly once for 12 months along with Elaprase at a dose of 5 mg if aged less than or equal to (<=) 8 months; 7.5 mg if aged greater than (>) 8 to 30 months and 10 mg if aged > 30 months to 3 years. |
| COMPLETED |
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| NOT COMPLETED |
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Intent to treat (ITT) population included all randomized participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | No IT Treatment | Participants aged 3 to < 18 years received Elaprase therapy as standard of care for 12 months. |
| BG001 | IT Treatment | Participants aged 3 to < 18 years received IT injections of 10 mg Idursulfase-IT once monthly for 12 months through SOPH-A-PORT Mini S IDDD along with Elaprase. |
| BG002 | Substudy | Participants aged less than 3 years received Idursulfase-IT monthly once for 12 months along with Elaprase at a dose of 5 mg if aged <= 8 months; 7.5 mg if aged > 8 to 30 months and 10 mg if aged > 30 months to 3 years. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | 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. | ITT population with number of participants evaluable for this outcome measure. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline, Week 52 |
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| Secondary | 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. | ITT population with number of participants evaluable for this outcome measure. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline, Week 52 |
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| Secondary | 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. | ITT population included all randomized participants. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline, Week 16, Week 28 and Week 40 |
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| Secondary | 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. | ITT population included all randomized participants. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline, Week 16, Week 28 and Week 40 |
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| Secondary | 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). | ITT population included all randomized participants. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline, Week 16, Week 28, Week 40 and Week 52 |
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| Secondary | 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. | ITT population included all randomized participants. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline, Week 16, Week 28, Week 40 and Week 52 |
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| Secondary | 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. | ITT population with number of participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Week 16, Week 28, Week 40 and Week 52 |
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| Secondary | 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". | ITT population with number of participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Week 16, Week 28, Week 40 and Week 52 |
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| Secondary | 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. | ITT population with number of participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Percentage of chronological age | Baseline, Week 16, Week 28, Week 40 and Week 52 |
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| Secondary | 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". | ITT population with number of participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Percentage of chronological age | Baseline, Week 16, Week 28, Week 40 and Week 52 |
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| Secondary | 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. | ITT population with number of participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | T-score | Baseline, Week 16, Week 28, Week 40 and Week 52 |
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| Secondary | 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". | ITT population with number of participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Week 16, Week 28, Week 40 and Week 52 |
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| Secondary | 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. | ITT population included all randomized participants. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Week 16, Week 28, Week 40 and Week 52 |
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| Secondary | 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. | ITT population included all randomized participants. | Posted | Mean | Standard Deviation | Percentage of chronological age | Baseline, Week 16, Week 28, Week 40 and Week 52 |
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| Secondary | 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. | ITT population included all randomized participants. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Week 16, Week 28, Week 40 and Week 52 |
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| Secondary | 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. | ITT population included all randomized participants. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Week 16, Week 28, Week 40 and Week 52 |
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| Secondary | 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. | ITT population included all randomized participants. | Posted | Count of Participants | Participants | Baseline, Week 16, Week 28, Week 40 and Week 52 |
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| Secondary | Maximum Observed Drug Concentration (Cmax) of Idursulfase After IT Administration | The Cmax of idursulfase after IT administration was reported. | Pharmacokinetic (PK) population included all participants who received investigational product and participated in the scheduled PK studies, and for whom at least 1 post-dose PK blood sample was collected. PK population with number of participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Nanogram per milliliter (ng/mL) | Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48 |
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| Secondary | Time to Reach Maximum Drug Concentration (Tmax) of Idursulfase After IT Administration | The tmax of idursulfase after IT administration was reported. | PK population with number of participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Hour (h) | Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48 |
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| Secondary | 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. | PK population with number of participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Nanogram*hour per milliliter (ng*h/mL) | Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48 |
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| Secondary | Terminal Half-life (t1/2) of Idursulfase After IT Administration | The t1/2 of idursulfase after IT administration was reported. | PK population with number of participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Hour (h) | Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48 |
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| Secondary | 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. | PK population with number of participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Liter per hour (L/h) | Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48 |
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| Secondary | 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. | PK population with number of participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Nanogram per milliliter (ng/mL) | Baseline, Week 52 |
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| Secondary | Concentration of Idursulfase in Cerebrospinal Fluid (CSF) | CSF samples were collected via the IDDD or lumbar puncture prior to the injection of Idursulfase-IT. | PK population with number of participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | ng/mL | Pre-dose on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 |
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| Secondary | 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. | ITT population included all randomized participants. | Posted | Count of Participants | Participants | Week 52 |
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| Secondary | 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). | Safety population included all randomized participants with any post-randomization safety assessments, analyzed according to the treatment received. | Posted | Count of Participants | Participants | From start of study treatment up to Week 53 |
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| Secondary | 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. | Substudy population included all participants enrolled and treated with investigational product in the substudy. | Posted | Number | Score on a scale | Baseline up to Week 52 |
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| Secondary | 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. | Substudy population included all participants enrolled and treated with investigational product in the substudy. | Posted | Number | Percentile score | Baseline up to Week 52 |
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| Secondary | 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. | Substudy population included all participants enrolled and treated with investigational product in the substudy. | Posted | Number | Score on a scale | Baseline up to Week 52 |
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| Secondary | 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. | Substudy population included all participants enrolled and treated with investigational product in the substudy. | Posted | Number | Months | Baseline up to Week 52 |
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| Secondary | 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. | Substudy population included all participants enrolled and treated with investigational product in the substudy. | Posted | Number | Percentage of chronological age | Baseline up to Week 52 |
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| Secondary | 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. | Substudy population included all participants enrolled and treated with investigational product in the substudy. | Posted | Number | score on a scale | Baseline up to Week 52 |
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From start of study treatment up to Week 53
For IT Treatment group 34 participants were randomized but only 33 participants are part of the safety population as 1 participant discontinued the study without receiving study treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | No IT Treatment | Participants aged 3 to < 18 years received Elaprase therapy as standard of care for 12 months. | 0 | 15 | 2 | 15 | 14 | 15 |
| EG001 | IT Treatment | Participants aged 3 to < 18 years received IT injections of 10 mg Idursulfase-IT once monthly for 12 months through SOPH-A-PORT Mini S IDDD along with Elaprase. | 0 | 33 | 12 | 33 | 33 | 33 |
| EG002 | Substudy | Participants aged less than 3 years received Idursulfase-IT monthly once for 12 months along with Elaprase at a dose of 5 mg if aged <= 8 months; 7.5 mg if aged > 8 to 30 months and 10 mg if aged > 30 months to 3 years. | 0 | 9 | 7 | 9 | 9 | 9 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension | Vascular disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Asthenia | General disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Device dislocation | General disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Device failure | General disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Device kink | General disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Fatigue | General disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Hyperthermia | General disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Hypothermia | General disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Implant site effusion | General disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Inflammation | General disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Pyrexia | General disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Vascular complication associated with device | General disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Bacteraemia | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
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| Catheter site cellulitis | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
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| Device related infection | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
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| Implant site infection | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
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| Meningitis bacterial | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
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| Respiratory syncytial virus infection | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
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| Stenotrophomonas infection | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
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| Tonsillitis | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
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| Wound infection | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
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| Procedural nausea | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
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| Procedural pain | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
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| Procedural vomiting | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
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| Pseudomeningocele | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
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| Wound dehiscence | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
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| CSF cell count increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
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| Cerebrospinal fluid leakage | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypochromasia | Blood and lymphatic system disorders | MedDRA 16.1 | Non-systematic Assessment |
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| Leukocytosis | Blood and lymphatic system disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Foot deformity | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Joint stiffness | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Knee deformity | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Kyphosis | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Muscle tightness | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Spinal disorder | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Spondylolysis | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Toe walking | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Trigger finger | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Diastolic hypertension | Vascular disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Diastolic hypotension | Vascular disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Systolic hypertension | Vascular disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Motion sickness | Ear and labyrinth disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Otorrhoea | Ear and labyrinth disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Astigmatism | Eye disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Conjunctivitis | Eye disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Excessive eye blinking | Eye disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Frequent bowel movements | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Perianal erythema | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Swollen tongue | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Teething | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Catheter site oedema | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Catheter site pain | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Catheter site swelling | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Device breakage | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Device component issue | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Device dislocation | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Device kink | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Device occlusion | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Discomfort | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Hyperthermia | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Implant site effusion | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Implant site pain | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Implant site swelling | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Irritability | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Medical device complication | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Medical device pain | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Puncture site pain | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Vascular complication associated with device | General disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Congenital osteodystrophy | Congenital, familial and genetic disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Dilatation ventricular | Cardiac disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Allergy to animal | Immune system disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Adenovirus infection | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Atypical pneumonia | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Ear infection fungal | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Fungal infection | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Gastrointestinal infection | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Hand-Foot-And-Mouth disease | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Localised infection | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Metapneumovirus infection | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Nail infection | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Otitis media acute | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Periodontitis | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Pharyngitis streptococcal | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Tinea infection | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Tinea pedis | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Viral pharyngitis | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Viral rash | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Excoriation | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Incision site erythema | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Incision site oedema | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Incision site pain | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Procedural headache | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Procedural hypertension | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Procedural hypotension | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Procedural nausea | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Procedural vomiting | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Pseudomeningocele | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Scar | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Thermal burn | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Wound secretion | Injury, poisoning and procedural complications | MedDRA 16.1 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Albumin CSF increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Bacterial test positive | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Blood alkaline phosphatase decreased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Blood calcium decreased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Blood pressure diastolic decreased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Blood pressure diastolic increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Blood pressure increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Blood pressure systolic decreased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Blood pressure systolic increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Blood thyroid stimulating hormone increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Blood triglycerides increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Body temperature decreased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Body temperature increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| CSF cell count increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| CSF glucose decreased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| CSF mononuclear cell count increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| CSF pressure increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| CSF protein increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| CSF white blood cell count increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Cardiac murmur | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Coagulation time prolonged | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Eosinophil count increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Eosinophil percentage increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Gamma-Glutamyltransferase increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Haematocrit decreased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Heart rate decreased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Heart rate increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Lymphocyte count increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Mean cell volume decreased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Monocyte count increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Neutrophil count increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Nuclear magnetic resonance imaging abnormal | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Nuclear magnetic resonance imaging brain abnormal | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Oxygen saturation decreased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Protein total decreased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Red blood cell count decreased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Red blood cells CSF positive | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Respiratory rate decreased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Respiratory rate increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Urine leukocyte esterase positive | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| White blood cell count increased | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| White blood cells urine positive | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| X-Ray abnormal | Investigations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Polyuria | Renal and urinary disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Hepatomegaly | Hepatobiliary disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Iron deficiency | Metabolism and nutrition disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Carpal tunnel syndrome | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Cerebrospinal fluid leakage | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Drooling | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Intracranial pressure increased | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Psychomotor hyperactivity | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Subdural effusion | Nervous system disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Abnormal behaviour | Psychiatric disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Affect lability | Psychiatric disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Aggression | Psychiatric disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Communication disorder | Psychiatric disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Dysphemia | Psychiatric disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Impulsive behaviour | Psychiatric disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Self injurious behaviour | Psychiatric disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Sleep disorder | Psychiatric disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Social avoidant behaviour | Psychiatric disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Pulmonary congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Blister | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Dermatitis diaper | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Generalised erythema | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Red man syndrome | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Scab | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Non-systematic Assessment |
|
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonmentor termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
| Prot_000.pdf |
| Prot | Yes | No | No | Study Protocol: Amendment 1 | Aug 14, 2013 | Sep 27, 2018 | Prot_001.pdf |
| Prot | Yes | No | No | Study Protocol: Amendment 2 | Dec 16, 2013 | Sep 27, 2018 | Prot_002.pdf |
| Prot | Yes | No | No | Study Protocol: Amendment 3 | Feb 9, 2015 | Sep 27, 2018 | Prot_003.pdf |
| Prot | Yes | No | No | Study Protocol: Amendment 4 | Dec 21, 2015 | Sep 27, 2018 | Prot_004.pdf |
| Prot | Yes | No | No | Study Protocol: Amendment 5 | Apr 18, 2016 | Sep 27, 2018 | Prot_005.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 9, 2017 | Sep 27, 2018 | SAP_006.pdf |
| ID | Term |
|---|---|
| D016532 | Mucopolysaccharidosis II |
| D013398 | Sudden Infant Death |
| D016464 | Lysosomal Storage Diseases |
| ID | Term |
|---|---|
| D038901 | X-Linked Intellectual Disability |
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D009083 | Mucopolysaccharidoses |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D017520 | Mucinoses |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D003645 | Death, Sudden |
| D003643 | Death |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D066088 | Infant Death |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Black or African American |
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| White |
|
| Other |
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