Mucopolysaccharidosis (MPS), Sanfilippo Syndrome
Conditions
Brief summary
This extension study will allow participants to continue receiving treatment with HGT-1410 and to initiate treatment in patients who received no-treatment in Study HGT-SAN-093, and will evaluate the long-term safety and efficacy of the study drug.
Interventions
DRUGHGT-1410
HGT-1410 administered according to Patient Group assignment.
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Months to 48 Months
Healthy volunteers
No
Inclusion criteria
Patients must meet all of the following criteria to be considered eligible for enrollment: 1. Patient has completed through at least the Week 48 visit of Study HGT-SAN-093 2. The patient's parent(s) or legally authorized guardian(s) must have voluntarily signed an Institutional Review Board- (IRB-)/ Independent Ethics Committee- (IEC-) 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, as relevant, must be obtained
Exclusion criteria
Patients will be excluded from the study if any of the following criteria are met: 1. The patient, if randomized to treatment in Study HGT-SAN-093, has experienced a decline of more than 20 points in the BSID-III cognitive DQ score between Baseline and the Week 48 visit in Study HGT-SAN-093, AND, upon individual evaluation by the Investigator, has been deemed a treatment failure\* 2. The patient has experienced, in the opinion of the Investigator, a safety or medical issue that contraindicates treatment with HGT-1410, including but not limited to clinically relevant intracranial hypertension, severe infusion-related reactions after treatment with HGT-1410, uncontrollable seizure disorder 3. The patient has a known hypersensitivity to any of the components of HGT-1410 4. The patient is enrolled in another clinical study, other than HGT-SAN-093, that involves clinical investigations or use of any investigational product (drug or \[intrathecal/spinal\] device) within 30 days prior to study enrollment or at any time during the study 5. The patient has any known or suspected hypersensitivity to anesthesia or is thought to be at an unacceptably high risk for anesthesia due to airway compromise or other conditions 6. The patient has a condition that is contraindicated as described in the SOPH-A-PORT® Mini S IDDD Instructions for Use, including: 1. The patient has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT ® Mini S device 2. The patient's body size is too small to support the size of the SOPH-A-PORT ® Mini S Access Port, as judged by the Investigator 3. The patient's drug therapy requires substances known to be incompatible with the materials of construction 4. The patient has a known or suspected local or general infection 5. The patient is at risk of abnormal bleeding due to a medical condition or therapy 6. The patient has one or more spinal abnormalities that could complicate safe implantation or fixation 7. The patient has a functioning CSF shunt device 8. The patient has shown an intolerance to an implanted device 7. The patient is unable to comply with the protocol (eg, is unable to return for safety evaluations, or is otherwise unlikely to complete the study) as determined by the Investigator * All treated patients in Study HGT-SAN-093 will have their cognitive development assessed at the Week 48 Visit in Study HGT-SAN-093. If a decline from Baseline of 20 points or less in the BSID-III DQ score is observed, then the patient may proceed into the Study SHP-610-201 without further evaluation. If a decline from Baseline of more than 20 points in DQ score is observed, then an individual evaluation by the Investigator will occur to determine if the patient is a treatment failure. This individual evaluation will take into account the DQ scores, VABS-II score, physical status, and any other information available for that patient at that time. If the Investigator deems the patient to be a treatment failure, then the patient may not enter the Study SHP-610-201
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Levels of Glycosaminoglycan (GAG) Concentration in Urine | Up to Week 120 | Levels of GAG concentration in Urine were reported. Last measurable data was presented for respective participant up to their last available time point. |
| Area Under Curve (AUC) of Recombinant Human Heparan N-Sulfatase (rhHNS) Concentration in Cerebro Spinal Fluid (CSF) | Week 0 and 48 | No sufficient pharmacokinetic (PK) samples were collected and analyzed due to early termination of the study. |
| Area Under Curve (AUC) of Recombinant Human Heparan N-Sulfatase (rhHNS) Concentration in Serum | Week 0, 48 and 96 | No sufficient PK samples were collected and analyzed due to early termination of the study. |
| Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) | Up to Week 120 | Levels of GAG concentration in CSF was reported. Last measurable data was presented for respective participant up to their last observed time point. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | From start of study drug administration up to follow-up (Week 276) | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered as a pharmaceutical product that did not necessarily have a causal relationship with this treatment. TEAEs was defined as all AEs from the time of initial IDDD implantation (or first dose if earlier) in either Study NCT02060526 (HGT-SAN-093) or Study NCT02350816 (SHP-610-210) to the data cutoff date (28 Jun 2017), or 30 days after the date of the last dose or 2 weeks after the date of device explant (whichever was later) if early termination occurred. Treatment-emergent AEs were summarized by type (serious, life-threatening), severity (mild, moderate, severe) and degree of relationship to investigational product (Intrathecal Drug Delivery Device (IDDD), device surgical procedure, or intraThecal administration of HGT-1410). |
| Number of Participants With Positive Anti-Recombinant Human Heparan N-Sulfatase (rhHNS) Antibody Status in Serum | Up to 120 weeks | Number of participants with positive anti-rhHNS antibody status in serum were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Developmental Quotient (DQ) Assessed by Neurocognitive Tests | Baseline, Week 120 | The development quotient (DQ) was 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). Higher scores are indicative of decreased development. Neurocognitive tests included Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), Kaufman Assessment Battery for Children, Second Edition (KABC-II), Vineland Adaptive Behavior Scales, Second Edition (VABS-II). Due to the premature termination of the treatment period, efficacy data were not analyzed and no efficacy conclusions were drawn. |
| Change From Baseline in Total Cortical Grey Matter Volume | Baseline, Week 120 | The total cortical grey matter volume was assessed by volumetric magnetic resonance imaging (MRI) of the brain. Due to the premature termination of the treatment period, efficacy data were not analyzed and no efficacy conclusions were drawn. |
| Change From Baseline Vineland Adaptive Behavior Scales Second Edition (VABS-II) | Baseline, Week 120 | 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 was 'Usually' = 2, 'Sometimes'/Partially' = 1 or 'Never' = 0. The raw scores was converted to domain standard scores (mean 100, SD 15). Higher scores indicate undesirable behavior. Due to the premature termination of the treatment period, efficacy data were not analyzed and no efficacy conclusions were drawn. |
Countries
France, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Participant flow
Recruitment details
The first participant enrolled in the study on 08 April 2015 and last participant last follow-up on 12 April 2019.
Pre-assignment details
A total of 17 participants were enrolled and completed treatment period in the study.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 milligrams (mg) administered intrathecally (IT) via IT drug delivery device (IDDD) every 2 weeks (Q2W) started at Week 50, with a cumulative treatment period of up to 42 months (168 weeks). | 7 |
| Group 2 Participants continued HGT-1410 treatment from HGT-SAN-093 (NCT02350816) study at a dose of 45 mg administered intrathecally IDDD every 4 weeks (Q4W) started at Week 52, with a cumulative treatment period of up to 42 months (168 weeks). | 6 |
| Group 3A Participants in Group 3A were not treated in HGT-SAN-093 (NCT02350816) study. Participants received HGT-1410 treatment at a dose of 45mg administered intrathecally IDDD Q2W started at Week 0 of the current extension study (SHP610-201=2014-003960-20), with a cumulative treatment period of up to 30 months (120 weeks). | 2 |
| Group 3B Participants in Group 3B were not treated in HGT-SAN-093 (NCT02350816) study. Participants received HGT-1410 treatment at a dose of 45mg administered intrathecally via IDDD Q4W started at Week 0 of the current extension study (SHP610-201=2014-003960-20), with a cumulative treatment period of up to 30 months (120 weeks). | 2 |
| Total | 17 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | Group 3A | Group 3B | Total |
|---|---|---|---|---|---|
| Age, Continuous | 29.64 Months STANDARD_DEVIATION 9.989 | 31.62 Months STANDARD_DEVIATION 8.598 | 40.40 Months STANDARD_DEVIATION 5.798 | 36.95 Months STANDARD_DEVIATION 7.142 | 32.47 Months STANDARD_DEVIATION 8.941 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 5 Participants | 2 Participants | 2 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 6 Participants | 2 Participants | 2 Participants | 17 Participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 2 Participants | 0 Participants | 10 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 0 Participants | 2 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 6 | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 7 / 7 | 6 / 6 | 2 / 2 | 2 / 2 |
| serious Total, serious adverse events | 6 / 7 | 6 / 6 | 0 / 2 | 1 / 2 |
Outcome results
Primary
Area Under Curve (AUC) of Recombinant Human Heparan N-Sulfatase (rhHNS) Concentration in Cerebro Spinal Fluid (CSF)
No sufficient pharmacokinetic (PK) samples were collected and analyzed due to early termination of the study.
Time frame: Week 0 and 48
Population: No sufficient PK samples were collected and analyzed due to early termination of the study.
Primary
Area Under Curve (AUC) of Recombinant Human Heparan N-Sulfatase (rhHNS) Concentration in Serum
No sufficient PK samples were collected and analyzed due to early termination of the study.
Time frame: Week 0, 48 and 96
Population: No sufficient pharmacokinetic (PK) samples were collected and analyzed due to early termination of the study.
Primary
Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF)
Levels of GAG concentration in CSF was reported. Last measurable data was presented for respective participant up to their last observed time point.
Time frame: Up to Week 120
Population: Safety population consisted of all participants who had the IDDD implant or received at least 1 dose of investigational product in the extension study (SHP610-201 \[NCT02350816\]). Here the number of participants analyzed signifies participants who were evaluable for this measure at specific category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) | Participant 14: Week 62 | 4.05 micromoles (μmol) |
| Group 1 | Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) | Participant 15: Week 60 | 1.63 micromoles (μmol) |
| Group 1 | Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) | Participant 6: Week 72 | 2.62 micromoles (μmol) |
| Group 1 | Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) | Participant 11: Week 60 | 1.35 micromoles (μmol) |
| Group 1 | Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) | Participant 12: Week 96 | 0.491 micromoles (μmol) |
| Group 1 | Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) | Participant 13: Week 84 | 2.84 micromoles (μmol) |
| Group 1 | Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) | Participant 3: Week 86 | 0.698 micromoles (μmol) |
| Group 2 | Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) | Participant 8: Week 72 | 2.49 micromoles (μmol) |
| Group 2 | Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) | Participant 2: Week 60 | 1.52 micromoles (μmol) |
| Group 2 | Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) | Participant 4: Week 72 | 1.5 micromoles (μmol) |
| Group 2 | Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) | Participant 7: Week 120 | 1.26 micromoles (μmol) |
| Group 2 | Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) | Participant 9: Week 72 | 1.77 micromoles (μmol) |
| Group 2 | Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) | Participant 10: Week 72 | 2.13 micromoles (μmol) |
| Group 3A | Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) | Participant 16: Week 20 | 0.699 micromoles (μmol) |
| Group 3A | Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) | Participant 5: Week 44 | 0.592 micromoles (μmol) |
| Group 3B | Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) | Participant 17: Week 8 | 2.59 micromoles (μmol) |
| Group 3B | Levels of Glycosaminoglycan (GAG) Concentration in Cerebro Spinal Fluid (CSF) | Participant 1: Week 16 | 3.67 micromoles (μmol) |
Primary
Levels of Glycosaminoglycan (GAG) Concentration in Urine
Levels of GAG concentration in Urine were reported. Last measurable data was presented for respective participant up to their last available time point.
Time frame: Up to Week 120
Population: Safety population consisted of all participants who had the IDDD implant or received at least 1 dose of investigational product in the extension study (SHP610-201 \[NCT02350816\]). Here the number of participants analyzed signifies participants who were evaluable for this measure at specific category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | Levels of Glycosaminoglycan (GAG) Concentration in Urine | Participant 14: Week 62 | 61.047755556 percentage of GAG |
| Group 1 | Levels of Glycosaminoglycan (GAG) Concentration in Urine | Participant 15: Week 60 | 40.230919792 percentage of GAG |
| Group 1 | Levels of Glycosaminoglycan (GAG) Concentration in Urine | Participant 6: Week 72 | 41.417183858 percentage of GAG |
| Group 1 | Levels of Glycosaminoglycan (GAG) Concentration in Urine | Participant 11: Week 60 | 41.011940047 percentage of GAG |
| Group 1 | Levels of Glycosaminoglycan (GAG) Concentration in Urine | Participant 12: Week 96 | 24.508878333 percentage of GAG |
| Group 1 | Levels of Glycosaminoglycan (GAG) Concentration in Urine | Participant 13: Week 84 | 11.31179 percentage of GAG |
| Group 1 | Levels of Glycosaminoglycan (GAG) Concentration in Urine | Participant 3: Week 86 | 23.814294737 percentage of GAG |
| Group 2 | Levels of Glycosaminoglycan (GAG) Concentration in Urine | Participant 8: Week 72 | 41.442593994 percentage of GAG |
| Group 2 | Levels of Glycosaminoglycan (GAG) Concentration in Urine | Participant 2: Week 60 | 36.6 percentage of GAG |
| Group 2 | Levels of Glycosaminoglycan (GAG) Concentration in Urine | Participant 4: Week 72 | 33.220498513 percentage of GAG |
| Group 2 | Levels of Glycosaminoglycan (GAG) Concentration in Urine | Participant 7: Week 120 | 126.08093356 percentage of GAG |
| Group 2 | Levels of Glycosaminoglycan (GAG) Concentration in Urine | Participant 9: Week 72 | 33.736917544 percentage of GAG |
| Group 2 | Levels of Glycosaminoglycan (GAG) Concentration in Urine | Participant 10: Week 72 | 21.063333103 percentage of GAG |
| Group 3A | Levels of Glycosaminoglycan (GAG) Concentration in Urine | Participant 16: Week 20 | 38.608023285 percentage of GAG |
| Group 3A | Levels of Glycosaminoglycan (GAG) Concentration in Urine | Participant 5: Week 44 | 31.266295955 percentage of GAG |
| Group 3B | Levels of Glycosaminoglycan (GAG) Concentration in Urine | Participant 17: Week 8 | 39.247789595 percentage of GAG |
| Group 3B | Levels of Glycosaminoglycan (GAG) Concentration in Urine | Participant 1: Week 16 | 48.562684655 percentage of GAG |
Primary
Number of Participants With Positive Anti-Recombinant Human Heparan N-Sulfatase (rhHNS) Antibody Status in Serum
Number of participants with positive anti-rhHNS antibody status in serum were reported.
Time frame: Up to 120 weeks
Population: Safety population consisted of all participants who had the IDDD implant or received at least 1 dose of investigational product in the extension study (SHP610-201 \[NCT02350816\]). The last observed time point data was presented for outcome measure data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Number of Participants With Positive Anti-Recombinant Human Heparan N-Sulfatase (rhHNS) Antibody Status in Serum | 7 Participants |
| Group 2 | Number of Participants With Positive Anti-Recombinant Human Heparan N-Sulfatase (rhHNS) Antibody Status in Serum | 6 Participants |
| Group 3A | Number of Participants With Positive Anti-Recombinant Human Heparan N-Sulfatase (rhHNS) Antibody Status in Serum | 2 Participants |
| Group 3B | Number of Participants With Positive Anti-Recombinant Human Heparan N-Sulfatase (rhHNS) Antibody Status in Serum | 2 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered as a pharmaceutical product that did not necessarily have a causal relationship with this treatment. TEAEs was defined as all AEs from the time of initial IDDD implantation (or first dose if earlier) in either Study NCT02060526 (HGT-SAN-093) or Study NCT02350816 (SHP-610-210) to the data cutoff date (28 Jun 2017), or 30 days after the date of the last dose or 2 weeks after the date of device explant (whichever was later) if early termination occurred. Treatment-emergent AEs were summarized by type (serious, life-threatening), severity (mild, moderate, severe) and degree of relationship to investigational product (Intrathecal Drug Delivery Device (IDDD), device surgical procedure, or intraThecal administration of HGT-1410).
Time frame: From start of study drug administration up to follow-up (Week 276)
Population: Safety population consisted of all participants who had the IDDD implant or received at least 1 dose of investigational product in the extension study (SHP610-201 \[NCT02350816\]).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Severe TEAEs | 3 Participants |
| Group 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Moderate TEAEs | 4 Participants |
| Group 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Mild TEAEs | 0 Participants |
| Group 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with TEAEs | 7 Participants |
| Group 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with IT Administration Related TEAEs | 3 Participants |
| Group 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with IDDD Related TEAEs | 5 Participants |
| Group 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Surgery Related TEAEs | 6 Participants |
| Group 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Serious TEAEs | 6 Participants |
| Group 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with HGT-1410 Related TEAEs | 5 Participants |
| Group 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Life-Threatening TEAEs | 0 Participants |
| Group 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Serious TEAEs | 6 Participants |
| Group 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with TEAEs | 6 Participants |
| Group 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Life-Threatening TEAEs | 0 Participants |
| Group 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Mild TEAEs | 0 Participants |
| Group 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Moderate TEAEs | 4 Participants |
| Group 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Severe TEAEs | 2 Participants |
| Group 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with HGT-1410 Related TEAEs | 5 Participants |
| Group 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Surgery Related TEAEs | 6 Participants |
| Group 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with IDDD Related TEAEs | 6 Participants |
| Group 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with IT Administration Related TEAEs | 6 Participants |
| Group 3A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Life-Threatening TEAEs | 0 Participants |
| Group 3A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Severe TEAEs | 9 Participants |
| Group 3A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Serious TEAEs | 0 Participants |
| Group 3A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with HGT-1410 Related TEAEs | 1 Participants |
| Group 3A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Surgery Related TEAEs | 1 Participants |
| Group 3A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with TEAEs | 2 Participants |
| Group 3A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with IT Administration Related TEAEs | 0 Participants |
| Group 3A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Mild TEAEs | 1 Participants |
| Group 3A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with IDDD Related TEAEs | 0 Participants |
| Group 3A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Moderate TEAEs | 1 Participants |
| Group 3B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Moderate TEAEs | 1 Participants |
| Group 3B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with IDDD Related TEAEs | 1 Participants |
| Group 3B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Surgery Related TEAEs | 1 Participants |
| Group 3B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Severe TEAEs | 9 Participants |
| Group 3B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Serious TEAEs | 1 Participants |
| Group 3B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Mild TEAEs | 1 Participants |
| Group 3B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with Life-Threatening TEAEs | 0 Participants |
| Group 3B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with HGT-1410 Related TEAEs | 1 Participants |
| Group 3B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with TEAEs | 2 Participants |
| Group 3B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Type, Severity and Relationship to Treatment Drug | Participants with IT Administration Related TEAEs | 1 Participants |
Secondary
Change From Baseline in the Developmental Quotient (DQ) Assessed by Neurocognitive Tests
The development quotient (DQ) was 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). Higher scores are indicative of decreased development. Neurocognitive tests included Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), Kaufman Assessment Battery for Children, Second Edition (KABC-II), Vineland Adaptive Behavior Scales, Second Edition (VABS-II). Due to the premature termination of the treatment period, efficacy data were not analyzed and no efficacy conclusions were drawn.
Time frame: Baseline, Week 120
Population: No participant was analyzed due to the premature termination of the treatment period of this study.
Secondary
Change From Baseline in Total Cortical Grey Matter Volume
The total cortical grey matter volume was assessed by volumetric magnetic resonance imaging (MRI) of the brain. Due to the premature termination of the treatment period, efficacy data were not analyzed and no efficacy conclusions were drawn.
Time frame: Baseline, Week 120
Population: No participant was analyzed due to the premature termination of the treatment period of this study.
Secondary
Change From Baseline Vineland Adaptive Behavior Scales Second Edition (VABS-II)
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 was 'Usually' = 2, 'Sometimes'/Partially' = 1 or 'Never' = 0. The raw scores was converted to domain standard scores (mean 100, SD 15). Higher scores indicate undesirable behavior. Due to the premature termination of the treatment period, efficacy data were not analyzed and no efficacy conclusions were drawn.
Time frame: Baseline, Week 120
Population: No participant was analyzed due to the premature termination of the treatment period of this study.