Sanfilippo Syndrome
Conditions
Keywords
Recombinant Human Heparan N-Sulfatase (rhHNS), Sanfilippo Syndrome Type A (MPS IIIA), Lysosomal storage disease (LSD), Mucopolysaccharidosis (MPS) III
Brief summary
Sanfilippo syndrome, or Mucopolysaccharidosis (MPS) III, is a rare lysosomal storage disease (LSD) caused by loss in activity of 1 of 9 enzymes necessary for degradation of the glycosaminoglycan (GAG) heparan sulfate (HS) in lysosomes. MPS IIIA results from deficiency of the enzyme heparan N-sulfatase (sulfamidase). In the absence of this enzyme, intermediates of the HS degradation process accumulate in the lysosomes of neurons and glial cells, with lesser accumulation outside the brain. MPS IIIA symptoms arise on average at 7 months of age, with the average age of diagnosis at 4.5 years for the majority of patients. Patients present a wide spectrum and severity of clinical symptoms. The central nervous system (CNS) is the most severely affected organ system in patients with MPS IIIA, evidenced by deficits in language development, motor skills, and intellectual development. In addition, there are abnormal behaviors including but not limited to aggression and excess motor activity/hyperactivity that contribute to disturbances in sleep.Overall, individuals with MPS IIIA have a marked developmental delay and significantly reduced lifespan to 15 years of age on average. The purpose of this study is to collect long term safety and tolerability data in patients with MPS IIIA who previously received rhHNS in study HGT-SAN-055 (NCT01155778).
Detailed description
No effective, disease-modifying therapies are currently approved as treatments for this devastating and disabling disease. Shire Human Genetic Therapies (Shire HGT) is developing a sulfamidase enzyme replacement therapy (ERT)rhHNS for patients with MPS IIIA. rhHNS is being administered into the cerebrospinal fluid (CSF) via an surgically implanted intrathecal drug delivery device (IDDD), because when administered intravenously (IV) it does not cross the blood brain barrier (BBB). This is a multicenter study designed to collect long-term safety and tolerability data in patients with Sanfilippo Syndrome Type A (MPS IIIA) who received rhHNS via a surgically implanted intrathecal drug delivery device (IDDD) in study HGT-SAN-055 and elected to continue therapy.Patients will continue in the treatment group as they participated in the HGT-SAN-055 study (rhHNS administered by IT injection 10 mg once per month, 45 mg once per month or 90 mg once per month. The study duration will be a maximum duration of 8 years of rhHNS treatment or until rhHNS is commercially available, the patient discontinues from the study, the Sponsor stops the study, or the Sponsor discontinues the development of rhHNS.
Interventions
BIOLOGICALrhHNS-10 mg
Once per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years
BIOLOGICALrhHNS-45 mg
Once per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years
BIOLOGICALrhHNS-90 mg
Once per month via an Intrathecal Drug Delivery Device (IDDD) for a maximum of 8 years
Sponsors
Shire
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients must meet all of the following criteria to be considered eligible for enrollment: 1. The patient must have completed Study HGT SAN 055 and the opinion of the investigator, has no safety or medical issues that contraindicate participation. 2. The patient, patient's parent(s), or legally authorized representative(s) has 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 with the patient's, the patient's, patient's parents or legally authorized representative's consent and patient's assent, as appropriate, must be obtained prior to any study specific procedures. 3. The patient has received at least 5 of the 6 planned infusions of rhHNS in the HGT-SAN-055 study. 4. Patients must be medically stable, in the opinion of the Investigator, to accommodate the protocol requirements, including travel, assessments, and IDDD surgery (if necessary for replacement purposes), without placing an undue burden on the patient/patient's family.
Exclusion criteria
Subjects will be excluded from the study if there is evidence of any of the following criteria at screening or at anytime during the study: 1. The patient has experienced an adverse reaction to study drug in Study HGT-SAN-55 that contraindicates further treatment with rhHNS. 2. The patient has a known hypersensitivity to the active ingredient or any excipients in rhHNS drug product. 3. The patient has significant non-MPS IIIA related central nervous system (CNS) impairment or behavioral disturbances that would confound the scientific integrity or interpretation of study assessments, as determined by the Investigator. 4. The patient has significant MPS IIIA behavioral-related issues, as determined by the Investigator, which would preclude performance of study neurocognitive and developmental testing procedures. 5. The patient is pregnant, breast feeding, or is a female patient of childbearing potential, who will not or cannot comply with the use of an acceptable method of birth control, such as condoms, barrier method, oral contraception, etc. 6. The patient has any known or suspected hypersensitivity to anesthesia or is thought to have an unacceptably high risk for anesthesia due to airway compromise or other conditions. 7. The patient has a history of poorly controlled seizure disorder. 8. The patient is currently receiving psychotropic or other medications, which in the Investigator's opinion, would be likely to substantially confound test results and the dose and regimen of which cannot be kept constant throughout the study. 9. The patient cannot sustain absence from aspirin, non-steroidal medications, or medications that affect blood clotting within 1 week prior to a relevant study-related procedure (eg, device re-implantation if applicable), or has ingested such medications within 1 week before any procedures in which any change in clotting activity would be deleterious. 10. The patient has received treatment with any investigational drug (other than rhHNS) intended as a treatment for MPS IIIA within the 30 days prior to, or during the study, or is currently enrolled in another study that involves an investigational drug or device (screening through safety follow-up contact). 11. The patient has received a hematopoietic stem cell or bone marrow transplant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | From start of study drug administration up to follow-up (Month 103) | 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. Treatment-emergent Adverse events (TEAEs) were defined as all adverse events (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. TEAEs included participants with any AE, any drug-related AE, any surgery-related AE, any IDDD-related AE, and any IT administration process-related AE, any SAE, any serious drug-related AE. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity | From start of study drug administration up to follow-up (Month 103) | 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. |
| Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | From start of study drug administration up to follow-up (Month 103) | Clinical laboratory assessments include hematology, serum chemistry including liver function tests, coagulation urinalysis and cerebrospinal fluid (CSF) were reported. |
| Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as Treatment Emergent Adverse Events (TEAEs) | From start of study drug administration up to follow-up (Month 103) | Any change in ECG assessments which were deemed to be clinically significant findings and abnormalities were recorded as TEAEs. |
| Number of Participants With Postive Anti-rhHNS Antibody Status in Serum by Recombinant Human Heparan N-Sulfatase (rhHNS) | Month 103 | 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. |
| Number of Participants With Positive Anti-rhHNS Antibody Status in Cerebrospinal Fluid (CSF) by Recombinant Human Heparan N-Sulfatase (rhHNS) | Month 103 | Antibody titers were determined for the samples that tested positive for anti-rhHNS antibodies. Participants with positive anti-rhHNS antibody in CSF were reported |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Baseline, Month 103 | 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. |
| Change From Baseline in Brain Magnetic Resonance Imaging (MRI) at Month 103 | Baseline, Month 103 | 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. |
| Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III)/Kaufman Assessment Battery for Children Second Edition (KABC-II) Age-Equivalent Scores at Month 103 | Baseline, Month 103 | 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. |
| Change From Baseline in Developmental Quotient (DQ) Using Bayley Scales of Infant Development Third Edition (BSID-III) and Kaufman Assessment Battery for Children Second Edition (KABC-II) at Month 103 | Baseline, Month 103 | 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. |
| Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Baseline, Month 103 | 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 Cerebrospinal Fluid (CSF) Total Heparan Sulfate Levels at Month 103 | Baseline, Month 103 | Change from baseline in CSF total heparan sulfate at month 103 was recorded. |
| Change From Baseline in Urine Glycosaminoglycan (GAG) Levels at Month 103 | Baseline, Month 103 | Change from baseline in Urine GAG at month 103 was recorded. |
Countries
Netherlands, United Kingdom
Participant flow
Recruitment details
The study was conducted at 2 study centers in the Netherlands and United Kingdom between 01 March 2011 (first participant first visit) and 12 April 2019 (last participant last visit).
Pre-assignment details
A total of 12 participants were enrolled in this extension study (HGT-SAN-067 \[NCT01299727\]), with 4 participants included in each of the 3 dose groups. Out of them, 10 participants completed the treatment period of the study.
Participants by arm
| Arm | Count |
|---|---|
| HGT-1410/rhHNS 10 mg Participants received HGT-1410/Recombinant human heparan N-sulfatase (rhHNS) 10 milligram (mg) for every 4 weeks (Q4W) via an intrathecal drug delivery device (IDDD). | 4 |
| HGT-1410/rhHNS 45 mg Participants received HGT-1410/rhHNS 45 mg for Q4W via IDDD. | 4 |
| HGT-1410/rhHNS 90 mg Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD. | 4 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Completed the Treatment Period | 3 | 4 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | HGT-1410/rhHNS 10 mg | HGT-1410/rhHNS 45 mg | HGT-1410/rhHNS 90 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 9.145 years STANDARD_DEVIATION 4.6956 | 9.070 years STANDARD_DEVIATION 9.7916 | 10.638 years STANDARD_DEVIATION 8.6645 | 9.618 years STANDARD_DEVIATION 7.2941 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 3 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 3 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 4 / 4 | 4 / 4 | 4 / 4 |
| serious Total, serious adverse events | 4 / 4 | 4 / 4 | 3 / 4 |
Outcome results
Primary
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as Treatment Emergent Adverse Events (TEAEs)
Any change in ECG assessments which were deemed to be clinically significant findings and abnormalities were recorded as TEAEs.
Time frame: From start of study drug administration up to follow-up (Month 103)
Population: 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).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HGT-1410/rhHNS 10 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as Treatment Emergent Adverse Events (TEAEs) | 0 Participants |
| HGT-1410/rhHNS 45 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as Treatment Emergent Adverse Events (TEAEs) | 0 Participants |
| HGT-1410/rhHNS 90 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as Treatment Emergent Adverse Events (TEAEs) | 0 Participants |
Primary
Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
Clinical laboratory assessments include hematology, serum chemistry including liver function tests, coagulation urinalysis and cerebrospinal fluid (CSF) were reported.
Time frame: From start of study drug administration up to follow-up (Month 103)
Population: 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).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HGT-1410/rhHNS 10 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Urinalysis | 0 Participants |
| HGT-1410/rhHNS 10 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Hematology | 2 Participants |
| HGT-1410/rhHNS 10 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Cerebrospinal fluid (CSF) | 3 Participants |
| HGT-1410/rhHNS 10 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Serum Chemistry | 1 Participants |
| HGT-1410/rhHNS 45 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Urinalysis | 1 Participants |
| HGT-1410/rhHNS 45 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Serum Chemistry | 4 Participants |
| HGT-1410/rhHNS 45 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Cerebrospinal fluid (CSF) | 4 Participants |
| HGT-1410/rhHNS 45 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Hematology | 0 Participants |
| HGT-1410/rhHNS 90 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Cerebrospinal fluid (CSF) | 0 Participants |
| HGT-1410/rhHNS 90 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Hematology | 1 Participants |
| HGT-1410/rhHNS 90 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Serum Chemistry | 1 Participants |
| HGT-1410/rhHNS 90 mg | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs) | Urinalysis | 1 Participants |
Primary
Number of Participants With Positive Anti-rhHNS Antibody Status in Cerebrospinal Fluid (CSF) by Recombinant Human Heparan N-Sulfatase (rhHNS)
Antibody titers were determined for the samples that tested positive for anti-rhHNS antibodies. Participants with positive anti-rhHNS antibody in CSF were reported
Time frame: Month 103
Population: 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).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HGT-1410/rhHNS 10 mg | Number of Participants With Positive Anti-rhHNS Antibody Status in Cerebrospinal Fluid (CSF) by Recombinant Human Heparan N-Sulfatase (rhHNS) | 0 Participants |
| HGT-1410/rhHNS 45 mg | Number of Participants With Positive Anti-rhHNS Antibody Status in Cerebrospinal Fluid (CSF) by Recombinant Human Heparan N-Sulfatase (rhHNS) | 0 Participants |
| HGT-1410/rhHNS 90 mg | Number of Participants With Positive Anti-rhHNS Antibody Status in Cerebrospinal Fluid (CSF) by Recombinant Human Heparan N-Sulfatase (rhHNS) | 0 Participants |
Primary
Number of Participants With Postive Anti-rhHNS Antibody Status in Serum by Recombinant Human Heparan N-Sulfatase (rhHNS)
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.
Time frame: Month 103
Population: 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).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HGT-1410/rhHNS 10 mg | Number of Participants With Postive Anti-rhHNS Antibody Status in Serum by Recombinant Human Heparan N-Sulfatase (rhHNS) | 0 Participants |
| HGT-1410/rhHNS 45 mg | Number of Participants With Postive Anti-rhHNS Antibody Status in Serum by Recombinant Human Heparan N-Sulfatase (rhHNS) | 0 Participants |
| HGT-1410/rhHNS 90 mg | Number of Participants With Postive Anti-rhHNS Antibody Status in Serum by Recombinant Human Heparan N-Sulfatase (rhHNS) | 0 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs)
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. Treatment-emergent Adverse events (TEAEs) were defined as all adverse events (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. TEAEs included participants with any AE, any drug-related AE, any surgery-related AE, any IDDD-related AE, and any IT administration process-related AE, any SAE, any serious drug-related AE.
Time frame: From start of study drug administration up to follow-up (Month 103)
Population: 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).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HGT-1410/rhHNS 10 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Partcipants with at least 1 HGT-1410 Related TEAEs | 4 Participants |
| HGT-1410/rhHNS 10 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Participants with at least IT Related TEAEs | 3 Participants |
| HGT-1410/rhHNS 10 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Participants with at least 1 IDDD Related TEAEs | 4 Participants |
| HGT-1410/rhHNS 10 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Participants with at least one TEAEs | 4 Participants |
| HGT-1410/rhHNS 10 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Participants with Drug Related Serious TEAEs | 0 Participants |
| HGT-1410/rhHNS 10 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Participants with at least 1 Serious TEAEs | 4 Participants |
| HGT-1410/rhHNS 10 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Participants with at least 1 Surgery Related TEAEs | 4 Participants |
| HGT-1410/rhHNS 45 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Participants with at least 1 IDDD Related TEAEs | 4 Participants |
| HGT-1410/rhHNS 45 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Participants with at least one TEAEs | 4 Participants |
| HGT-1410/rhHNS 45 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Partcipants with at least 1 HGT-1410 Related TEAEs | 4 Participants |
| HGT-1410/rhHNS 45 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Participants with at least 1 Surgery Related TEAEs | 4 Participants |
| HGT-1410/rhHNS 45 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Participants with at least IT Related TEAEs | 3 Participants |
| HGT-1410/rhHNS 45 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Participants with at least 1 Serious TEAEs | 4 Participants |
| HGT-1410/rhHNS 45 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Participants with Drug Related Serious TEAEs | 0 Participants |
| HGT-1410/rhHNS 90 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Participants with at least IT Related TEAEs | 2 Participants |
| HGT-1410/rhHNS 90 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Partcipants with at least 1 HGT-1410 Related TEAEs | 2 Participants |
| HGT-1410/rhHNS 90 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Participants with Drug Related Serious TEAEs | 0 Participants |
| HGT-1410/rhHNS 90 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Participants with at least 1 Serious TEAEs | 3 Participants |
| HGT-1410/rhHNS 90 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Participants with at least 1 IDDD Related TEAEs | 4 Participants |
| HGT-1410/rhHNS 90 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Participants with at least 1 Surgery Related TEAEs | 3 Participants |
| HGT-1410/rhHNS 90 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs) | Participants with at least one TEAEs | 4 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity
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.
Time frame: From start of study drug administration up to follow-up (Month 103)
Population: 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).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HGT-1410/rhHNS 10 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity | Participants with Moderate TEAEs | 4 Participants |
| HGT-1410/rhHNS 10 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity | Participants with Mild TEAEs | 4 Participants |
| HGT-1410/rhHNS 10 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity | Participants with Severe TEAEs | 1 Participants |
| HGT-1410/rhHNS 45 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity | Participants with Moderate TEAEs | 4 Participants |
| HGT-1410/rhHNS 45 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity | Participants with Mild TEAEs | 4 Participants |
| HGT-1410/rhHNS 45 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity | Participants with Severe TEAEs | 2 Participants |
| HGT-1410/rhHNS 90 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity | Participants with Mild TEAEs | 4 Participants |
| HGT-1410/rhHNS 90 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity | Participants with Severe TEAEs | 2 Participants |
| HGT-1410/rhHNS 90 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity | Participants with Moderate TEAEs | 3 Participants |
Secondary
Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103
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.
Time frame: Baseline, Month 103
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HGT-1410/rhHNS 10 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Expressive: Baseline | 22.00 Score on a scale | — |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Receptive: Baseline | 17.00 Score on a scale | — |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Fine Motor: Baseline | 25.00 Score on a scale | — |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Cognitive: Baseline | 19.00 Score on a scale | — |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Gross Motor: Baseline | 21.00 Score on a scale | — |
| HGT-1410/rhHNS 45 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Gross Motor: Baseline | 26.67 Score on a scale | Standard Deviation 13.868 |
| HGT-1410/rhHNS 45 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Cognitive: Baseline | 23.33 Score on a scale | Standard Deviation 12.097 |
| HGT-1410/rhHNS 45 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Receptive: Baseline | 24.00 Score on a scale | Standard Deviation 16.093 |
| HGT-1410/rhHNS 45 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Expressive: Baseline | 26.00 Score on a scale | Standard Deviation 13.528 |
| HGT-1410/rhHNS 45 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Fine Motor: Baseline | 27.67 Score on a scale | Standard Deviation 12.423 |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Gross Motor: Change at Month 103 | -21.00 Score on a scale | — |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Cognitive: Baseline | 21.50 Score on a scale | Standard Deviation 0.707 |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Cognitive: Change at Month 103 | 3.0 Score on a scale | — |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Receptive: Baseline | 17.50 Score on a scale | Standard Deviation 2.121 |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Receptive: Change at Month 103 | 0.00 Score on a scale | — |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Expressive: Baseline | 22.50 Score on a scale | Standard Deviation 0.707 |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Expressive: Change at Month 103 | 0.00 Score on a scale | — |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Fine Motor: Baseline | 23.50 Score on a scale | Standard Deviation 2.121 |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Fine Motor: Change at Month 103 | 0.00 Score on a scale | — |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103 | Gross Motor: Baseline | 35.50 Score on a scale | Standard Deviation 9.192 |
Secondary
Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III)/Kaufman Assessment Battery for Children Second Edition (KABC-II) Age-Equivalent Scores at Month 103
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.
Time frame: Baseline, Month 103
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HGT-1410/rhHNS 10 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III)/Kaufman Assessment Battery for Children Second Edition (KABC-II) Age-Equivalent Scores at Month 103 | Baseline | 66.00 Score on a scale | Standard Deviation 66.468 |
| HGT-1410/rhHNS 45 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III)/Kaufman Assessment Battery for Children Second Edition (KABC-II) Age-Equivalent Scores at Month 103 | Baseline | 35.17 Score on a scale | Standard Deviation 21.678 |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III)/Kaufman Assessment Battery for Children Second Edition (KABC-II) Age-Equivalent Scores at Month 103 | Baseline | 60.90 Score on a scale | Standard Deviation 60.21 |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III)/Kaufman Assessment Battery for Children Second Edition (KABC-II) Age-Equivalent Scores at Month 103 | Change at Month 103 | 3.00 Score on a scale | — |
Secondary
Change From Baseline in Brain Magnetic Resonance Imaging (MRI) at Month 103
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.
Time frame: Baseline, Month 103
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HGT-1410/rhHNS 10 mg | Change From Baseline in Brain Magnetic Resonance Imaging (MRI) at Month 103 | GMV: Baseline | 550.50 milliliter (mL) | Standard Deviation 111.043 |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Brain Magnetic Resonance Imaging (MRI) at Month 103 | GMV: Change at Month 103 | -99.49 milliliter (mL) | — |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Brain Magnetic Resonance Imaging (MRI) at Month 103 | WMV: Baseline | 403.72 milliliter (mL) | Standard Deviation 105.575 |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Brain Magnetic Resonance Imaging (MRI) at Month 103 | WMV: Change at Month 103 | -33.19 milliliter (mL) | — |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Brain Magnetic Resonance Imaging (MRI) at Month 103 | ICSFV: Baseline | 26.152 milliliter (mL) | Standard Deviation 9.2975 |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Brain Magnetic Resonance Imaging (MRI) at Month 103 | ICSFV: Change at Month 103 | 18.753 milliliter (mL) | — |
| HGT-1410/rhHNS 45 mg | Change From Baseline in Brain Magnetic Resonance Imaging (MRI) at Month 103 | GMV: Baseline | 534.25 milliliter (mL) | Standard Deviation 117.291 |
| HGT-1410/rhHNS 45 mg | Change From Baseline in Brain Magnetic Resonance Imaging (MRI) at Month 103 | ICSFV: Baseline | 22.904 milliliter (mL) | Standard Deviation 20.8459 |
| HGT-1410/rhHNS 45 mg | Change From Baseline in Brain Magnetic Resonance Imaging (MRI) at Month 103 | WMV: Baseline | 348.28 milliliter (mL) | Standard Deviation 76.854 |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Brain Magnetic Resonance Imaging (MRI) at Month 103 | WMV: Baseline | 442.45 milliliter (mL) | Standard Deviation 79.814 |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Brain Magnetic Resonance Imaging (MRI) at Month 103 | GMV: Baseline | 600.28 milliliter (mL) | Standard Deviation 67.884 |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Brain Magnetic Resonance Imaging (MRI) at Month 103 | ICSFV: Baseline | 20.925 milliliter (mL) | Standard Deviation 15.9681 |
Secondary
Change From Baseline in Cerebrospinal Fluid (CSF) Total Heparan Sulfate Levels at Month 103
Change from baseline in CSF total heparan sulfate at month 103 was recorded.
Time frame: Baseline, Month 103
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HGT-1410/rhHNS 10 mg | Change From Baseline in Cerebrospinal Fluid (CSF) Total Heparan Sulfate Levels at Month 103 | Baseline | 5.775 micromoles (μmol) | Standard Deviation 3.465 |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Cerebrospinal Fluid (CSF) Total Heparan Sulfate Levels at Month 103 | Change at Month 103 | -4.010 micromoles (μmol) | — |
| HGT-1410/rhHNS 45 mg | Change From Baseline in Cerebrospinal Fluid (CSF) Total Heparan Sulfate Levels at Month 103 | Baseline | 4.710 micromoles (μmol) | Standard Deviation 2.968 |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Cerebrospinal Fluid (CSF) Total Heparan Sulfate Levels at Month 103 | Baseline | 3.795 micromoles (μmol) | Standard Deviation 1.611 |
Secondary
Change From Baseline in Developmental Quotient (DQ) Using Bayley Scales of Infant Development Third Edition (BSID-III) and Kaufman Assessment Battery for Children Second Edition (KABC-II) at Month 103
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.
Time frame: Baseline, Month 103
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HGT-1410/rhHNS 10 mg | Change From Baseline in Developmental Quotient (DQ) Using Bayley Scales of Infant Development Third Edition (BSID-III) and Kaufman Assessment Battery for Children Second Edition (KABC-II) at Month 103 | Baseline | 51.91 Score on a scale | Standard Deviation 27.292 |
| HGT-1410/rhHNS 45 mg | Change From Baseline in Developmental Quotient (DQ) Using Bayley Scales of Infant Development Third Edition (BSID-III) and Kaufman Assessment Battery for Children Second Edition (KABC-II) at Month 103 | Baseline | 43.24 Score on a scale | Standard Deviation 23.112 |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Developmental Quotient (DQ) Using Bayley Scales of Infant Development Third Edition (BSID-III) and Kaufman Assessment Battery for Children Second Edition (KABC-II) at Month 103 | Baseline | 51.87 Score on a scale | Standard Deviation 36.095 |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Developmental Quotient (DQ) Using Bayley Scales of Infant Development Third Edition (BSID-III) and Kaufman Assessment Battery for Children Second Edition (KABC-II) at Month 103 | Change at Month 103 | -10.96 Score on a scale | — |
Secondary
Change From Baseline in Urine Glycosaminoglycan (GAG) Levels at Month 103
Change from baseline in Urine GAG at month 103 was recorded.
Time frame: Baseline, Month 103
Population: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| HGT-1410/rhHNS 10 mg | Change From Baseline in Urine Glycosaminoglycan (GAG) Levels at Month 103 | NA microgram per milliliter (mcg/mL) |
| HGT-1410/rhHNS 45 mg | Change From Baseline in Urine Glycosaminoglycan (GAG) Levels at Month 103 | NA microgram per milliliter (mcg/mL) |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Urine Glycosaminoglycan (GAG) Levels at Month 103 | NA microgram per milliliter (mcg/mL) |
Secondary
Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103
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.
Time frame: Baseline, Month 103
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HGT-1410/rhHNS 10 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Socialization: Baseline | 64.3 Score on a scale | Standard Deviation 12.5 |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Motor Skills: Change at Month 103 | -18.0 Score on a scale | — |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Adaptive Behavior: Baseline | 63.3 Score on a scale | Standard Deviation 14.61 |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Daily Living: Baseline | 62.5 Score on a scale | Standard Deviation 15.52 |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Communication: Baseline | 68.3 Score on a scale | Standard Deviation 19.03 |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Daily Living: Change at Month 103 | -19.0 Score on a scale | — |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Adaptive Behavior:Change at Month 103 | -18.0 Score on a scale | — |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Socialization: Change at Month 103 | -15.0 Score on a scale | — |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Motor Skills: Baseline | 82.7 Score on a scale | Standard Deviation 29.77 |
| HGT-1410/rhHNS 10 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Communication: Change at Month 103 | -27.0 Score on a scale | — |
| HGT-1410/rhHNS 45 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Socialization: Baseline | 65.5 Score on a scale | Standard Deviation 32.42 |
| HGT-1410/rhHNS 45 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Adaptive Behavior: Baseline | 59.0 Score on a scale | Standard Deviation 26.96 |
| HGT-1410/rhHNS 45 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Communication: Baseline | 57.5 Score on a scale | Standard Deviation 25.94 |
| HGT-1410/rhHNS 45 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Daily Living: Baseline | 62.3 Score on a scale | Standard Deviation 27.58 |
| HGT-1410/rhHNS 45 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Motor Skills: Baseline | 76.3 Score on a scale | Standard Deviation 5.69 |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Motor Skills: Change at Month 103 | -14.0 Score on a scale | — |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Adaptive Behavior: Baseline | 59.5 Score on a scale | Standard Deviation 29.77 |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Adaptive Behavior:Change at Month 103 | -20.0 Score on a scale | — |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Communication: Baseline | 60.3 Score on a scale | Standard Deviation 30.86 |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Communication: Change at Month 103 | -20.0 Score on a scale | — |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Daily Living: Baseline | 60.0 Score on a scale | Standard Deviation 30 |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Daily Living: Change at Month 103 | -34.0 Score on a scale | — |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Socialization: Baseline | 58.7 Score on a scale | Standard Deviation 35.92 |
| HGT-1410/rhHNS 90 mg | Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103 | Motor Skills: Baseline | 72.5 Score on a scale | Standard Deviation 12.02 |