Trial Outcomes & Findings for Study of Long Term Safety and Clinical Outcomes of Idursulfase IT and Elaprase Treatment in Pediatric Participants Who Have Completed Study HGT-HIT-094 (NCT NCT02412787)

Participants took part in the study at various investigative sites in Australia, Canada, France, Mexico, Spain, the United Kingdom, and the United States of America (USA) from 14 April 2015 to 18 April 2024.

Participants who completed end of study (EOS) Visit Week 52 assessments of Study HGT-HIT-094 (NCT02055118) and who met the eligibility criteria were enrolled in this extension study. Some of the enrolled participants who were treated with idursulfase-IT in Study HGT-HIT-094 were analyzed as per the reference timepoints of HGT-HIT-094 study for some evaluations. For others, the reference timepoints after enrollment to the extension study were considered.

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

An AE is any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered investigational product-related.

Participants were assessed for clinically significant changes in vital signs like injection (IT) vital signs and regular vital signs (temperature, pulse, blood pressure \[systolic and diastolic\], oxygen saturation, and respiration rate).

Participants were assessed for clinically significant changes in laboratory parameters such as chemistry, hematology, urinalysis and cerebrospinal fluid (CSF) values.

Participants were assessed for clinically significant changes in 12-lead ECG findings (such as heart rate, PR interval, QRS interval, QT interval, and the corrected QT interval).

Idursulfase concentrations in serum were determined using a validated Enzyme -Linked Immunosorbent Assay (ELISA) method. Concentration for Cmax is presented in this endpoint.

The percent change in concentration of GAG in CSF was assessed. GAGs are long sugar chains that are like building blocks for the body's tissues, especially connective tissues like cartilage, skin, and tendons, and play a crucial role in cell signaling and interactions.

The percent change in concentration of GAG in urine was assessed. GAGs are long sugar chains that are like building blocks for the body's tissues, especially connective tissues like cartilage, skin, and tendons, and play a crucial role in cell signaling and interactions.

DAS-II was used to assess all participants of age 2 years, 6 months or older. DAS-II comprises 2 overlapping batteries. Early Years battery (EYB) was designed for children ages 2 years, 6 months through 6 years, 11 months. The School Age Battery (SAB) was designed for children ages 7 years, 0 months through 17 years, 11months. These batteries are fully co-normed for ages 5 years, 0 months, through 8 years, 11 months. The cluster areas include general conceptual ability (GCA), verbal, nonverbal, spatial, and special nonverbal composite (SNC). The cluster area score represents a score (mean=100 and standard deviation=15) on which higher scores indicate higher level of cognitive ability.

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 \[ABC\] (a composite of the other 4 domains). The standard scores for four key domains were mean=100 and standard deviation=15, where higher scores indicate a higher level of cognitive ability. Positive change from baseline indicates improvement in adaptive functioning. The ABC score (a composite of the other 4 domains) ranges from 20 to 160 on which higher scores indicate a higher level of adaptive functioning. A positive change from baseline value indicates improvement in adaptive functioning.

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 ABC (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.

DAS-II comprises 2 overlapping batteries; EYB= 2 years,6 months through 6 years,11 months and SAB=7 years,0 months through 17 years,11 months. Core subtests include Verbal Comprehension, Picture Similarities, Naming Vocabulary, Pattern Construction, Matrices and Copying for DAS-II Early Years and Recall of Designs, Word Definitions, Pattern Construction, Matrices, Verbal Similarities, and Sequential and Quantitative Reasoning for DAS-II School Years. Standard subtests scores (mean=50 and standard deviation of 10) for each subtest were converted to age equivalent scores (AES). Higher AES indicates greater cognitive ability. Negative change from baseline indicates worsening.

DAS-II was used to assess all participants of age 2 years,6 months or older.DAS-II comprises 2 overlapping batteries.EYB was designed for children ages 2 years,6 months through 6 years,11 months.SAB was designed for children ages 7 years,0 months through 17 years,11 months.Core subtests include Verbal Comprehension,Picture Similarities,Naming Vocabulary,Pattern Construction,Matrices, \& Copying for DAS-II Early Years\&Recall of Designs,Word Definitions, Pattern Construction,Matrices,Verbal Similarities, \& Sequential and Quantitative Reasoning for the DAS-II School Years. The DQ was computed as a ratio and expressed as a percentage using the AES divided by the age at testing (\[AES/chronological age\] × 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.

DAS-II was used to assess all participants of age 2 years, 6 months or older. DAS-II comprises 2 overlapping batteries. EYB was designed for children ages 2 years, 6 months through 6 years, 11 months. SAB was designed for children ages 7 years, 0 months through 17 years, 11months. The core subtests include Verbal Comprehension, Picture Similarities, Naming Vocabulary, Pattern Construction, Matrices, and Copying for the DAS-II Early Years and Recall of Designs, Word Definitions, Pattern Construction, Matrices, Verbal Similarities, and Sequential and Quantitative Reasoning for the DAS-II School Years. Core subtests score represent a score (mean = 50 and standard deviation of 10) on which higher scores indicate a higher level of cognitive ability.

The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following subdomains of 5 key domains: Communication (Receptive, Expressive, Written), Daily Living Skills(Personal, Domestic, Community), Socialization (Interpersonal Relationships, Play and Leisure Time, Coping Skills), Motor Skills (Gross, Fine). Standard subdomain scores (mean=100 and standard deviation of 15) for each subdomain were converted to AES. Higher AES indicates greater cognitive ability. Negative change from baseline indicates worsening.

The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following subdomains of 5 key domains: Communication (Receptive, Expressive, Written), Daily Living Skills (Personal, Domestic, Community), Socialization (Interpersonal Relationships, Play and Leisure Time, Coping Skills), Motor Skills (Gross, Fine). The DQ 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). Higher scores indicate better cognitive ability. A positive change from baseline value indicates improvement in cognition.

The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following subdomains of 5 key domains: Communication (Receptive, Expressive, Written), Daily Living Skills (Personal, Domestic, Community), Socialization (Interpersonal Relationships, Play and Leisure Time, Coping Skills), Motor Skills (Gross, Fine). The 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.

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 maladaptive behavior index is a composite of the internalizing, externalizing, and other types of undesirable behavior that may interfere with the individual's adaptive functioning. The v-Scale scores represent a score (mean = 15 and standard deviation of 3; range: 1-24) on which higher scores indicate a higher level of adaptive functioning.

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 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. Only categories having non-zero values are reported.

Brain structure volume was assessed from brain total intracranial volume, brain total tissue volume, brain total white matter, brain total gray matter, and total CSF volume as measured by MRI.

Data was not collected for this outcome measure due to Sponsor decision.

This pre-specified optional outcome measure was not assessed.

This pre-specified optional outcome measure was not assessed.