Once per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years

Once per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years

Any change in ECG assessments which were deemed to be clinically significant findings and abnormalities were recorded as TEAEs.

Antibody titers were determined for the samples that tested positive for anti-rhHNS antibodies. Participants with positive Anti-rhHNS antibody status in serum were reported.

Antibody titers were determined for the samples that tested positive for anti-rhHNS antibodies. Participants with positive anti-rhHNS antibody in CSF were reported

BSID-III was used to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers aged 0-42 months and consisted of a series of developmental play tasks. KABC-II was an individually administered measure of the processing and reasoning abilities of children and adolescents between the ages of 3 and 18 years and an alternative to BSID-III. Raw 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 (age norm; range: 0, unbound ). A positive value indicates improvement. The BSID--III and KABC--II age--equivalent scores were based on the cognitive domain and average non-verbal age-equivalent score, respectively.

BSID-III was used to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers aged 0-42 months and consisted of a series of developmental play tasks. KABC-II was an individually administered measure of the processing and reasoning abilities of children and adolescents between the ages of 3 and 18 years and an alternative to BSID-III. Raw scores of successfully completed items are converted to scale scores and to composite scores. The mean composite score is 100 and the standard deviation (SD) is 15. The DQ was a means to express a neurodevelopmental/cognitive delay which 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). A positive value indicates improvement in health and cognition.

VABS-II measured adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. It was an instrument that supports the diagnosis of intellectual and developmental disabilities in participants. This test measured 5 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other four domains). Scoring is 'Usually' = 2, 'Sometimes'/Partially' = 1 or 'Never' = 0. 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.

Change from baseline in CSF total heparan sulfate at month 103 was recorded.

Change from baseline in Urine GAG at month 103 was recorded.

Brain MRI parameters include grey matter volume (GMV), white matter volume (WMV) and Intracranial cerebrospinal fluid Volume (ICSFV). Change from baseline in brain MRI at Month 103 was reported.

Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD.

Total of all reporting groups

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 study drug related. TEAEs were defined as all AEs from the time of the surgery for first IDDD implantation or first dose of HGT-1410 in study HGT-SAN-055 (NCT01155778) to the data cutoff date, or 30 days after the date of the last dose or 2 weeks after the date of device explant if early termination occurred. Severity of an AE is determined by following definitions: Mild: No limitation of usual activities; Moderate: Some limitation of usual activities; Severe: Inability to carry out usual activities.

Safety population consisted of all eligible participants from Study HGT-SAN-055 (NCT01155778) who agreed to participate in this extension study, HGT-SAN-067 (NCT01299727).

Clinical laboratory assessments include hematology, serum chemistry including liver function tests, coagulation urinalysis and cerebrospinal fluid (CSF) were reported.

Safety population consisted of all eligible participants from Study HGT-SAN-055 (NCT01155778) who agreed to participate in this extension study, HGT-SAN-067 (NCT01299727).

Any change in ECG assessments which were deemed to be clinically significant findings and abnormalities were recorded as TEAEs.

Safety population consisted of all eligible participants from Study HGT-SAN-055 (NCT01155778) who agreed to participate in this extension study, HGT-SAN-067 (NCT01299727).

Antibody titers were determined for the samples that tested positive for anti-rhHNS antibodies. Participants with positive Anti-rhHNS antibody status in serum were reported.

Safety population consisted of all eligible participants from Study HGT-SAN-055 (NCT01155778) who agreed to participate in this extension study, HGT-SAN-067 (NCT01299727).

Antibody titers were determined for the samples that tested positive for anti-rhHNS antibodies. Participants with positive anti-rhHNS antibody in CSF were reported

Safety population consisted of all eligible participants from Study HGT-SAN-055 (NCT01155778) who agreed to participate in this extension study, HGT-SAN-067 (NCT01299727).

BSID-III was used to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers aged 0-42 months and consisted of a series of developmental play tasks. 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 denote stronger skills and abilities in the domain, indicating better outcomes.

Safety population consisted of all eligible participants from Study HGT-SAN-055 (NCT01155778) who agreed to participate in this extension study, HGT-SAN-067 (NCT01299727). Here, number of participants analyzed signifies participants who were evaluable for this outcome measure at the specific categories.

BSID-III was used to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers aged 0-42 months and consisted of a series of developmental play tasks. KABC-II was an individually administered measure of the processing and reasoning abilities of children and adolescents between the ages of 3 and 18 years and an alternative to BSID-III. Raw 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 (age norm; range: 0, unbound ). A positive value indicates improvement. The BSID--III and KABC--II age--equivalent scores were based on the cognitive domain and average non-verbal age-equivalent score, respectively.

Safety population consisted of all eligible participants from Study HGT-SAN-055 (NCT01155778) who agreed to participate in this extension study, HGT-SAN-067 (NCT01299727). Here, number of participants analyzed signifies participants who were evaluable for this outcome measure at the specific categories.

BSID-III was used to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers aged 0-42 months and consisted of a series of developmental play tasks. KABC-II was an individually administered measure of the processing and reasoning abilities of children and adolescents between the ages of 3 and 18 years and an alternative to BSID-III. Raw scores of successfully completed items are converted to scale scores and to composite scores. The mean composite score is 100 and the standard deviation (SD) is 15. The DQ was a means to express a neurodevelopmental/cognitive delay which 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). A positive value indicates improvement in health and cognition.

Safety population consisted of all eligible participants from Study HGT-SAN-055 (NCT01155778) who agreed to participate in this extension study, HGT-SAN-067 (NCT01299727). Here, number of participants analyzed signifies participants who were evaluable for this outcome measure at the specific categories.

VABS-II measured adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. It was an instrument that supports the diagnosis of intellectual and developmental disabilities in participants. This test measured 5 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other four domains). Scoring is 'Usually' = 2, 'Sometimes'/Partially' = 1 or 'Never' = 0. 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.

Safety population consisted of all eligible participants from Study HGT-SAN-055 (NCT01155778) who agreed to participate in this extension study, HGT-SAN-067 (NCT01299727). Here, number of participants analyzed signifies participants who were evaluable for this outcome measure at the specific categories.

Change from baseline in CSF total heparan sulfate at month 103 was recorded.

Safety population consisted of all eligible participants from Study HGT-SAN-055 (NCT01155778) who agreed to participate in this extension study, HGT-SAN-067 (NCT01299727). Here, the number of participants analyzed refer to the participants evaluable for this outcome measure at the specific categories.

Change from baseline in Urine GAG at month 103 was recorded.

Safety population consisted of all eligible participants from Study HGT-SAN-055 (NCT01155778) who agreed to participate in this extension study. Data was not collected for this outcome as the trial was early terminated due to pre-specified efficacy criteria were not met.

Brain MRI parameters include grey matter volume (GMV), white matter volume (WMV) and Intracranial cerebrospinal fluid Volume (ICSFV). Change from baseline in brain MRI at Month 103 was reported.

Safety population consisted of all eligible participants from Study HGT-SAN-055 (NCT01155778) who agreed to participate in this extension study, HGT-SAN-067 (NCT01299727). Here, the number of participants analyzed refer to the participants evaluable for this outcome measure at the specific categories.

Participants received HGT-1410/rhHNS 45 mg for Q4W via IDDD.

Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD.