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Extension of Study HGT-SAN-055 Evaluating Administration of rhHNS in Patients With Sanfilippo Syndrome Type A (MPS IIIA)

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ClinicalTrials.gov Identifier: NCT01299727
Recruitment Status : Terminated (Completion of follow-up period)
First Posted : February 18, 2011
Results First Posted : April 21, 2020
Last Update Posted : April 21, 2020
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Sanfilippo Syndrome
Interventions Biological: rhHNS-10 mg
Biological: rhHNS-45 mg
Biological: rhHNS-90 mg
Enrollment 12
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.
Arm/Group Title HGT-1410/rhHNS 10 mg HGT-1410/rhHNS 45 mg HGT-1410/rhHNS 90 mg
Hide Arm/Group Description 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). Participants received HGT-1410/rhHNS 45 mg for Q4W via IDDD. Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD.
Period Title: Overall Study
Started 4 4 4
Completed 0 0 0
Not Completed 4 4 4
Reason Not Completed
Withdrawal by Subject             1             0             0
Adverse Event             0             0             1
Completed the Treatment Period             3             4             3
Arm/Group Title HGT-1410/rhHNS 10 mg HGT-1410/rhHNS 45 mg HGT-1410/rhHNS 90 mg Total
Hide Arm/Group Description 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). Participants received HGT-1410/rhHNS 45 mg for Q4W via IDDD. Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD. Total of all reporting groups
Overall Number of Baseline Participants 4 4 4 12
Hide Baseline Analysis Population Description
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). Baseline visit for this study was the first day the participant received their first dose of HGT-1410 in Study HGT-SAN-055 (NCT01155778).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 4 participants 4 participants 12 participants
9.145  (4.6956) 9.070  (9.7916) 10.638  (8.6645) 9.618  (7.2941)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 4 participants 12 participants
Female
1
  25.0%
2
  50.0%
1
  25.0%
4
  33.3%
Male
3
  75.0%
2
  50.0%
3
  75.0%
8
  66.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 4 participants 12 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
4
 100.0%
4
 100.0%
4
 100.0%
12
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 4 participants 12 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
  25.0%
1
  25.0%
2
  16.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
4
 100.0%
3
  75.0%
3
  75.0%
10
  83.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs) And Treatment Emergent Serious Adverse Events (TESAEs)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HGT-1410/rhHNS 10 mg HGT-1410/rhHNS 45 mg HGT-1410/rhHNS 90 mg
Hide Arm/Group Description:
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).
Participants received HGT-1410/rhHNS 45 mg for Q4W via IDDD.
Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD.
Overall Number of Participants Analyzed 4 4 4
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with at least one TEAEs
4
 100.0%
4
 100.0%
4
 100.0%
Partcipants with at least 1 HGT-1410 Related TEAEs
4
 100.0%
4
 100.0%
2
  50.0%
Participants with at least 1 Surgery Related TEAEs
4
 100.0%
4
 100.0%
3
  75.0%
Participants with at least 1 IDDD Related TEAEs
4
 100.0%
4
 100.0%
4
 100.0%
Participants with at least IT Related TEAEs
3
  75.0%
3
  75.0%
2
  50.0%
Participants with at least 1 Serious TEAEs
4
 100.0%
4
 100.0%
3
  75.0%
Participants with Drug Related Serious TEAEs
0
   0.0%
0
   0.0%
0
   0.0%
2.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HGT-1410/rhHNS 10 mg HGT-1410/rhHNS 45 mg HGT-1410/rhHNS 90 mg
Hide Arm/Group Description:
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).
Participants received HGT-1410/rhHNS 45 mg for Q4W via IDDD.
Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD.
Overall Number of Participants Analyzed 4 4 4
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with Mild TEAEs
4
 100.0%
4
 100.0%
4
 100.0%
Participants with Moderate TEAEs
4
 100.0%
4
 100.0%
3
  75.0%
Participants with Severe TEAEs
1
  25.0%
2
  50.0%
2
  50.0%
3.Primary Outcome
Title Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HGT-1410/rhHNS 10 mg HGT-1410/rhHNS 45 mg HGT-1410/rhHNS 90 mg
Hide Arm/Group Description:
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).
Participants received HGT-1410/rhHNS 45 mg for Q4W via IDDD.
Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD.
Overall Number of Participants Analyzed 4 4 4
Measure Type: Count of Participants
Unit of Measure: Participants
Hematology
2
  50.0%
0
   0.0%
1
  25.0%
Serum Chemistry
1
  25.0%
4
 100.0%
1
  25.0%
Urinalysis
0
   0.0%
1
  25.0%
1
  25.0%
Cerebrospinal fluid (CSF)
3
  75.0%
4
 100.0%
0
   0.0%
4.Primary Outcome
Title Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as Treatment Emergent Adverse Events (TEAEs)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HGT-1410/rhHNS 10 mg HGT-1410/rhHNS 45 mg HGT-1410/rhHNS 90 mg
Hide Arm/Group Description:
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).
Participants received HGT-1410/rhHNS 45 mg for Q4W via IDDD.
Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD.
Overall Number of Participants Analyzed 4 4 4
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
5.Primary Outcome
Title Number of Participants With Postive Anti-rhHNS Antibody Status in Serum by Recombinant Human Heparan N-Sulfatase (rhHNS)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HGT-1410/rhHNS 10 mg HGT-1410/rhHNS 45 mg HGT-1410/rhHNS 90 mg
Hide Arm/Group Description:
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).
Participants received HGT-1410/rhHNS 45 mg for Q4W via IDDD.
Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD.
Overall Number of Participants Analyzed 4 4 4
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
6.Primary Outcome
Title Number of Participants With Positive Anti-rhHNS Antibody Status in Cerebrospinal Fluid (CSF) by Recombinant Human Heparan N-Sulfatase (rhHNS)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HGT-1410/rhHNS 10 mg HGT-1410/rhHNS 45 mg HGT-1410/rhHNS 90 mg
Hide Arm/Group Description:
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).
Participants received HGT-1410/rhHNS 45 mg for Q4W via IDDD.
Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD.
Overall Number of Participants Analyzed 4 4 4
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
7.Secondary Outcome
Title Change From Baseline in Bayley Scales of Infant Development Third Edition (BSID-III) at Month 103
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HGT-1410/rhHNS 10 mg HGT-1410/rhHNS 45 mg HGT-1410/rhHNS 90 mg
Hide Arm/Group Description:
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).
Participants received HGT-1410/rhHNS 45 mg for Q4W via IDDD.
Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD.
Overall Number of Participants Analyzed 1 3 2
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Cognitive: Baseline Number Analyzed 1 participants 3 participants 2 participants
19.00 [1]   (NA) 23.33  (12.097) 21.50  (0.707)
Cognitive: Change at Month 103 Number Analyzed 0 participants 0 participants 1 participants
3.0 [1]   (NA)
Receptive: Baseline Number Analyzed 1 participants 3 participants 2 participants
17.00 [1]   (NA) 24.00  (16.093) 17.50  (2.121)
Receptive: Change at Month 103 Number Analyzed 0 participants 0 participants 1 participants
0.00 [1]   (NA)
Expressive: Baseline Number Analyzed 1 participants 3 participants 2 participants
22.00 [1]   (NA) 26.00  (13.528) 22.50  (0.707)
Expressive: Change at Month 103 Number Analyzed 0 participants 0 participants 1 participants
0.00 [1]   (NA)
Fine Motor: Baseline Number Analyzed 1 participants 3 participants 2 participants
25.00 [1]   (NA) 27.67  (12.423) 23.50  (2.121)
Fine Motor: Change at Month 103 Number Analyzed 0 participants 0 participants 1 participants
0.00 [1]   (NA)
Gross Motor: Baseline Number Analyzed 1 participants 3 participants 2 participants
21.00 [1]   (NA) 26.67  (13.868) 35.50  (9.192)
Gross Motor: Change at Month 103 Number Analyzed 0 participants 0 participants 1 participants
-21.00 [1]   (NA)
[1]
Here, 'NA' indicates that the standard deviation was not calculated as only one participant was evaluated.
8.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HGT-1410/rhHNS 10 mg HGT-1410/rhHNS 45 mg HGT-1410/rhHNS 90 mg
Hide Arm/Group Description:
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).
Participants received HGT-1410/rhHNS 45 mg for Q4W via IDDD.
Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD.
Overall Number of Participants Analyzed 2 4 4
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Baseline Number Analyzed 2 participants 4 participants 4 participants
66.00  (66.468) 35.17  (21.678) 60.90  (60.210)
Change at Month 103 Number Analyzed 0 participants 0 participants 1 participants
3.00 [1]   (NA)
[1]
Here, 'NA' indicates that the standard deviation was not calculated as only one participant was evaluated.
9.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HGT-1410/rhHNS 10 mg HGT-1410/rhHNS 45 mg HGT-1410/rhHNS 90 mg
Hide Arm/Group Description:
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).
Participants received HGT-1410/rhHNS 45 mg for Q4W via IDDD.
Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD.
Overall Number of Participants Analyzed 2 4 4
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Baseline Number Analyzed 2 participants 4 participants 4 participants
51.91  (27.292) 43.24  (23.112) 51.87  (36.095)
Change at Month 103 Number Analyzed 0 participants 0 participants 1 participants
-10.96 [1]   (NA)
[1]
Here, 'NA' indicates that the standard deviation was not calculated as only one participant was evaluated.
10.Secondary Outcome
Title Change From Baseline in Vineland Adaptive Behavioral Scales Second Edition (VABS-II) at Month 103
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HGT-1410/rhHNS 10 mg HGT-1410/rhHNS 45 mg HGT-1410/rhHNS 90 mg
Hide Arm/Group Description:
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).
Participants received HGT-1410/rhHNS 45 mg for Q4W via IDDD.
Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD.
Overall Number of Participants Analyzed 4 4 4
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Adaptive Behavior: Baseline Number Analyzed 4 participants 4 participants 4 participants
63.3  (14.61) 59.0  (26.96) 59.5  (29.77)
Adaptive Behavior:Change at Month 103 Number Analyzed 1 participants 0 participants 1 participants
-18.0 [1]   (NA) -20.0 [1]   (NA)
Communication: Baseline Number Analyzed 4 participants 4 participants 4 participants
68.3  (19.03) 57.5  (25.94) 60.3  (30.86)
Communication: Change at Month 103 Number Analyzed 1 participants 0 participants 1 participants
-27.0 [1]   (NA) -20.0 [1]   (NA)
Daily Living: Baseline Number Analyzed 4 participants 4 participants 4 participants
62.5  (15.52) 62.3  (27.58) 60.0  (30.00)
Daily Living: Change at Month 103 Number Analyzed 1 participants 0 participants 1 participants
-19.0 [1]   (NA) -34.0 [1]   (NA)
Socialization: Baseline Number Analyzed 4 participants 4 participants 3 participants
64.3  (12.50) 65.5  (32.42) 58.7  (35.92)
Socialization: Change at Month 103 Number Analyzed 1 participants 0 participants 0 participants
-15.0 [1]   (NA)
Motor Skills: Baseline Number Analyzed 3 participants 3 participants 2 participants
82.7  (29.77) 76.3  (5.69) 72.5  (12.02)
Motor Skills: Change at Month 103 Number Analyzed 1 participants 0 participants 1 participants
-18.0 [1]   (NA) -14.0 [1]   (NA)
[1]
Here, 'NA' indicates that the standard deviation was not calculated as only one participant was evaluated.
11.Secondary Outcome
Title Change From Baseline in Cerebrospinal Fluid (CSF) Total Heparan Sulfate Levels at Month 103
Hide Description Change from baseline in CSF total heparan sulfate at month 103 was recorded.
Time Frame Baseline, Month 103
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HGT-1410/rhHNS 10 mg HGT-1410/rhHNS 45 mg HGT-1410/rhHNS 90 mg
Hide Arm/Group Description:
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).
Participants received HGT-1410/rhHNS 45 mg for Q4W via IDDD.
Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD.
Overall Number of Participants Analyzed 4 4 4
Mean (Standard Deviation)
Unit of Measure: micromoles (μmol)
Baseline Number Analyzed 4 participants 4 participants 4 participants
5.775  (3.465) 4.710  (2.968) 3.795  (1.611)
Change at Month 103 Number Analyzed 1 participants 0 participants 0 participants
-4.010 [1]   (NA)
[1]
Here, 'NA' indicates that the standard deviation was not calculated as only one participant was evaluated.
12.Secondary Outcome
Title Change From Baseline in Urine Glycosaminoglycan (GAG) Levels at Month 103
Hide Description Change from baseline in Urine GAG at month 103 was recorded.
Time Frame Baseline, Month 103
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HGT-1410/rhHNS 10 mg HGT-1410/rhHNS 45 mg HGT-1410/rhHNS 90 mg
Hide Arm/Group Description:
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).
Participants received HGT-1410/rhHNS 45 mg for Q4W via IDDD.
Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD.
Overall Number of Participants Analyzed 4 4 4
Mean (Standard Deviation)
Unit of Measure: microgram per milliliter (mcg/mL)
NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
[1]
Here, 'NA' indicates that the data was not collected due to early termination of the study.
13.Secondary Outcome
Title Change From Baseline in Brain Magnetic Resonance Imaging (MRI) at Month 103
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title HGT-1410/rhHNS 10 mg HGT-1410/rhHNS 45 mg HGT-1410/rhHNS 90 mg
Hide Arm/Group Description:
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).
Participants received HGT-1410/rhHNS 45 mg for Q4W via IDDD.
Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD.
Overall Number of Participants Analyzed 4 4 4
Mean (Standard Deviation)
Unit of Measure: milliliter (mL)
GMV: Baseline Number Analyzed 4 participants 4 participants 4 participants
550.50  (111.043) 534.25  (117.291) 600.28  (67.884)
GMV: Change at Month 103 Number Analyzed 1 participants 0 participants 0 participants
-99.49 [1]   (NA)
WMV: Baseline Number Analyzed 4 participants 4 participants 4 participants
403.72  (105.575) 348.28  (76.854) 442.45  (79.814)
WMV: Change at Month 103 Number Analyzed 1 participants 0 participants 0 participants
-33.19 [1]   (NA)
ICSFV: Baseline Number Analyzed 4 participants 4 participants 4 participants
26.152  (9.2975) 22.904  (20.8459) 20.925  (15.9681)
ICSFV: Change at Month 103 Number Analyzed 1 participants 0 participants 0 participants
18.753 [1]   (NA)
[1]
Here, 'NA' indicates that the standard deviation was not calculated as only one participant was evaluated.
Time Frame From start of study drug administration up to follow-up (Month 103).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title HGT-1410/rhHNS-10 mg HGT-1410/rhHNS-45 mg HGT-1410/rhHNS-90 mg
Hide Arm/Group Description 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). Participants received HGT-1410/rhHNS 45 mg for Q4W via IDDD. Participants received HGT-1410/rhHNS 90 mg for Q4W via IDDD.
All-Cause Mortality
HGT-1410/rhHNS-10 mg HGT-1410/rhHNS-45 mg HGT-1410/rhHNS-90 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/4 (0.00%)      0/4 (0.00%)      0/4 (0.00%)    
Hide Serious Adverse Events
HGT-1410/rhHNS-10 mg HGT-1410/rhHNS-45 mg HGT-1410/rhHNS-90 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/4 (100.00%)      4/4 (100.00%)      3/4 (75.00%)    
Blood and lymphatic system disorders       
Leukocytosis * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Ear and labyrinth disorders       
Auricular pseudocyst * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Gastrointestinal disorders       
Vomiting * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
General disorders       
Device breakage * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Device component issue * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Device failure * 1  2/4 (50.00%)  2 4/4 (100.00%)  6 2/4 (50.00%)  2
Device leakage * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Device material issue * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Pyrexia * 1  1/4 (25.00%)  1 1/4 (25.00%)  1 0/4 (0.00%)  0
Infections and infestations       
Central nervous system infection * 1  2/4 (50.00%)  2 1/4 (25.00%)  1 0/4 (0.00%)  0
Device related infection * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 1/4 (25.00%)  1
Epstein-Barr virus infection * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Implant site infection * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Lower respiratory tract infection * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Meningitis * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Postoperative wound infection * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Viral infection * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Injury, poisoning and procedural complications       
Accidental overdose * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Subdural haematoma * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Wound dehiscence * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Investigations       
CSF white blood cell count increased * 1  1/4 (25.00%)  1 1/4 (25.00%)  1 0/4 (0.00%)  0
Nervous system disorders       
Intracranial hypotension * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Surgical and medical procedures       
Medical device change * 1  3/4 (75.00%)  6 3/4 (75.00%)  5 1/4 (25.00%)  2
Medical device removal * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
1
Term from vocabulary, MedDRA 13.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
HGT-1410/rhHNS-10 mg HGT-1410/rhHNS-45 mg HGT-1410/rhHNS-90 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/4 (100.00%)      4/4 (100.00%)      4/4 (100.00%)    
Blood and lymphatic system disorders       
Anaemia * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Eosinophilia * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Lymphadenopathy * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Cardiac disorders       
Mitral valve incompetence * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Congenital, familial and genetic disorders       
Thalassaemia trait * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Ear and labyrinth disorders       
Ear canal erythema * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Ear pain * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  3
Middle ear effusion * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Otorrhoea * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Tympanic membrane disorder * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Tympanic membrane hyperaemia * 1  0/4 (0.00%)  0 1/4 (25.00%)  2 0/4 (0.00%)  0
Tympanic membrane perforation * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Eye disorders       
Lacrimation increased * 1  2/4 (50.00%)  2 0/4 (0.00%)  0 0/4 (0.00%)  0
Myopia * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Gastrointestinal disorders       
Abdominal pain upper * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 1/4 (25.00%)  1
Abnormal faeces * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Constipation * 1  2/4 (50.00%)  8 2/4 (50.00%)  2 2/4 (50.00%)  6
Defaecation urgency * 1  1/4 (25.00%)  2 0/4 (0.00%)  0 1/4 (25.00%)  1
Diarrhoea * 1  3/4 (75.00%)  10 3/4 (75.00%)  10 1/4 (25.00%)  1
Dysphagia * 1  1/4 (25.00%)  2 0/4 (0.00%)  0 0/4 (0.00%)  0
Eructation * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Faeces discoloured * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Gastrooesophageal reflux disease * 1  1/4 (25.00%)  1 1/4 (25.00%)  1 0/4 (0.00%)  0
Mouth ulceration * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 2/4 (50.00%)  2
Nausea * 1  2/4 (50.00%)  2 1/4 (25.00%)  1 1/4 (25.00%)  2
Regurgitation * 1  1/4 (25.00%)  1 1/4 (25.00%)  1 0/4 (0.00%)  0
Retching * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Salivary hypersecretion * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Vomiting * 1  3/4 (75.00%)  16 3/4 (75.00%)  23 3/4 (75.00%)  3
General disorders       
Administration site pain * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Catheter site erythema * 1  0/4 (0.00%)  0 1/4 (25.00%)  2 0/4 (0.00%)  0
Catheter site haemorrhage * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Catheter site inflammation * 1  1/4 (25.00%)  7 0/4 (0.00%)  0 0/4 (0.00%)  0
Catheter site pain * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Chills * 1  1/4 (25.00%)  1 1/4 (25.00%)  2 0/4 (0.00%)  0
Complication of device insertion * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Complication of device removal * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Device breakage * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Device failure * 1  1/4 (25.00%)  1 1/4 (25.00%)  3 0/4 (0.00%)  0
Device leakage * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Fatigue * 1  1/4 (25.00%)  4 2/4 (50.00%)  3 1/4 (25.00%)  1
Feeling hot * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Gait disturbance * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Implant site effusion * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Implant site swelling * 1  2/4 (50.00%)  4 3/4 (75.00%)  7 2/4 (50.00%)  3
Influenza like illness * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Irritability * 1  3/4 (75.00%)  4 0/4 (0.00%)  0 1/4 (25.00%)  2
Local swelling * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Malaise * 1  2/4 (50.00%)  17 1/4 (25.00%)  2 1/4 (25.00%)  7
Medical device complication * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Oedema peripheral * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Pain * 1  1/4 (25.00%)  1 1/4 (25.00%)  1 0/4 (0.00%)  0
Pyrexia * 1  4/4 (100.00%)  18 3/4 (75.00%)  31 3/4 (75.00%)  5
Immune system disorders       
Allergy to arthropod bite * 1  1/4 (25.00%)  3 0/4 (0.00%)  0 1/4 (25.00%)  5
Hypersensitivity * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 1/4 (25.00%)  2
Seasonal allergy * 1  1/4 (25.00%)  1 1/4 (25.00%)  1 0/4 (0.00%)  0
Infections and infestations       
Abscess oral * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Bronchitis * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Candida nappy rash * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Catheter site infection * 1  1/4 (25.00%)  6 0/4 (0.00%)  0 0/4 (0.00%)  0
Cellulitis * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Central nervous system infection * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Ear infection * 1  1/4 (25.00%)  1 2/4 (50.00%)  3 2/4 (50.00%)  12
Enterobiasis * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Fungal infection * 1  1/4 (25.00%)  2 1/4 (25.00%)  1 0/4 (0.00%)  0
Gastroenteritis * 1  2/4 (50.00%)  4 0/4 (0.00%)  0 0/4 (0.00%)  0
Helminthic infection * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Impetigo * 1  1/4 (25.00%)  2 0/4 (0.00%)  0 1/4 (25.00%)  1
Influenza * 1  1/4 (25.00%)  2 0/4 (0.00%)  0 1/4 (25.00%)  2
Lower respiratory tract infection * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Nasopharyngitis * 1  2/4 (50.00%)  7 3/4 (75.00%)  7 2/4 (50.00%)  4
Onychomycosis * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  2
Oral candidiasis * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Oral herpes * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  2
Otitis externa * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  4
Otitis media * 1  0/4 (0.00%)  0 2/4 (50.00%)  2 2/4 (50.00%)  3
Otitis media acute * 1  1/4 (25.00%)  3 0/4 (0.00%)  0 0/4 (0.00%)  0
Pharyngitis * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Pneumonia * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Post procedural infection * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Postoperative wound infection * 1  1/4 (25.00%)  2 1/4 (25.00%)  1 1/4 (25.00%)  2
Proteus infection * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Rhinitis * 1  4/4 (100.00%)  6 2/4 (50.00%)  14 3/4 (75.00%)  5
Staphylococcal infection * 1  0/4 (0.00%)  0 1/4 (25.00%)  2 0/4 (0.00%)  0
Tinea pedis * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Tonsillitis * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Upper respiratory tract infection * 1  3/4 (75.00%)  3 1/4 (25.00%)  2 1/4 (25.00%)  1
Urinary tract infection * 1  1/4 (25.00%)  2 1/4 (25.00%)  1 1/4 (25.00%)  1
Varicella * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Viral infection * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 1/4 (25.00%)  2
Viral rash * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Viral upper respiratory tract infection * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Wound infection staphylococcal * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Injury, poisoning and procedural complications       
Arthropod bite * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Contusion * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Drug toxicity * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Excoriation * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Fall * 1  1/4 (25.00%)  6 1/4 (25.00%)  1 2/4 (50.00%)  3
Feeding tube complication * 1  1/4 (25.00%)  2 0/4 (0.00%)  0 0/4 (0.00%)  0
Head injury * 1  1/4 (25.00%)  1 1/4 (25.00%)  1 1/4 (25.00%)  1
Nail injury * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Open wound * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Post procedural discomfort * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Procedural headache * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Procedural nausea * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Procedural pain * 1  3/4 (75.00%)  3 0/4 (0.00%)  0 1/4 (25.00%)  1
Procedural site reaction * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Procedural vomiting * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Scratch * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Skin laceration * 1  1/4 (25.00%)  1 2/4 (50.00%)  2 1/4 (25.00%)  1
Thermal burn * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Investigations       
Blood bicarbonate decreased * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Blood creatine phosphokinase increased * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Blood uric acid increased * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 1/4 (25.00%)  1
Body temperature increased * 1  1/4 (25.00%)  2 2/4 (50.00%)  5 2/4 (50.00%)  2
CSF protein increased * 1  1/4 (25.00%)  1 2/4 (50.00%)  2 0/4 (0.00%)  0
CSF white blood cell count increased * 1  2/4 (50.00%)  3 3/4 (75.00%)  3 0/4 (0.00%)  0
Haematocrit decreased * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Haemoglobin decreased * 1  1/4 (25.00%)  1 1/4 (25.00%)  2 0/4 (0.00%)  0
Lymphocyte count increased * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 1/4 (25.00%)  1
Mean cell haemoglobin decreased * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Mean cell volume decreased * 1  0/4 (0.00%)  0 1/4 (25.00%)  2 0/4 (0.00%)  0
Monocyte count decreased * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Neutrophil count decreased * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Norovirus test positive * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Red blood cells CSF positive * 1  0/4 (0.00%)  0 1/4 (25.00%)  3 0/4 (0.00%)  0
Serum ferritin decreased * 1  0/4 (0.00%)  0 1/4 (25.00%)  2 0/4 (0.00%)  0
Weight decreased * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
White blood cell count increased * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Metabolism and nutrition disorders       
Hyperphagia * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Iron deficiency * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Polydipsia * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Acquired claw toe * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Back pain * 1  0/4 (0.00%)  0 2/4 (50.00%)  3 1/4 (25.00%)  2
Growing pains * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Intervertebral disc protrusion * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Joint swelling * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Mobility decreased * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Musculoskeletal stiffness * 1  1/4 (25.00%)  2 0/4 (0.00%)  0 1/4 (25.00%)  1
Myalgia * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Pain in extremity * 1  1/4 (25.00%)  1 2/4 (50.00%)  2 0/4 (0.00%)  0
Scoliosis * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Synovial cyst * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Toe walking * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Trigger finger * 1  1/4 (25.00%)  2 0/4 (0.00%)  0 0/4 (0.00%)  0
Weight bearing difficulty * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Nervous system disorders       
Akathisia * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Balance disorder * 1  1/4 (25.00%)  2 0/4 (0.00%)  0 0/4 (0.00%)  0
Bulbar palsy * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Cauda equina syndrome * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  6
Cognitive disorder * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Crying * 1  2/4 (50.00%)  3 0/4 (0.00%)  0 0/4 (0.00%)  0
Dizziness * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Drooling * 1  2/4 (50.00%)  2 0/4 (0.00%)  0 0/4 (0.00%)  0
Dyskinesia * 1  1/4 (25.00%)  3 0/4 (0.00%)  0 0/4 (0.00%)  0
Head titubation * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Headache * 1  2/4 (50.00%)  13 1/4 (25.00%)  6 1/4 (25.00%)  91
Hyperreflexia * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Hypertonia * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Intracranial hypotension * 1  0/4 (0.00%)  0 2/4 (50.00%)  3 0/4 (0.00%)  0
Memory impairment * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Motor dysfunction * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Nervous system disorder * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Paraesthesia * 1  1/4 (25.00%)  12 1/4 (25.00%)  12 2/4 (50.00%)  9
Presyncope * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Psychomotor hyperactivity * 1  0/4 (0.00%)  0 2/4 (50.00%)  3 1/4 (25.00%)  1
Syncope * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Psychiatric disorders       
Abnormal behaviour * 1  0/4 (0.00%)  0 2/4 (50.00%)  3 1/4 (25.00%)  1
Anxiety * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 3/4 (75.00%)  3
Conversion disorder * 1  1/4 (25.00%)  2 0/4 (0.00%)  0 0/4 (0.00%)  0
Depressed mood * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 1/4 (25.00%)  1
Insomnia * 1  1/4 (25.00%)  1 1/4 (25.00%)  1 1/4 (25.00%)  1
Intentional self-injury * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Obsessive-compulsive disorder * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Restlessness * 1  2/4 (50.00%)  3 1/4 (25.00%)  2 1/4 (25.00%)  1
Sleep disorder * 1  2/4 (50.00%)  6 1/4 (25.00%)  1 0/4 (0.00%)  0
Stereotypy * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Renal and urinary disorders       
Enuresis * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Incontinence * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Micturition urgency * 1  1/4 (25.00%)  5 1/4 (25.00%)  4 1/4 (25.00%)  13
Urinary incontinence * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 1/4 (25.00%)  1
Reproductive system and breast disorders       
Dysmenorrhoea * 1  1/4 (25.00%)  3 0/4 (0.00%)  0 0/4 (0.00%)  0
Labia enlarged * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Penile adhesion * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Penile erythema * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Uterine haemorrhage * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Choking * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Cough * 1  4/4 (100.00%)  6 1/4 (25.00%)  2 2/4 (50.00%)  2
Epistaxis * 1  1/4 (25.00%)  10 1/4 (25.00%)  1 1/4 (25.00%)  7
Hyperventilation * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  2
Nasal congestion * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Oropharyngeal pain * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 2/4 (50.00%)  2
Pharyngeal erythema * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Rhinorrhoea * 1  3/4 (75.00%)  6 2/4 (50.00%)  5 2/4 (50.00%)  3
Skin and subcutaneous tissue disorders       
Dermatitis * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Dermatitis allergic * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Dermatitis diaper * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Dry skin * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  2
Eczema * 1  2/4 (50.00%)  3 1/4 (25.00%)  1 1/4 (25.00%)  2
Erythema * 1  0/4 (0.00%)  0 1/4 (25.00%)  3 0/4 (0.00%)  0
Hyperkeratosis * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Onycholysis * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Pruritus * 1  1/4 (25.00%)  1 1/4 (25.00%)  1 0/4 (0.00%)  0
Pruritus generalised * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Rash * 1  1/4 (25.00%)  2 1/4 (25.00%)  1 1/4 (25.00%)  1
Rash macular * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Rosacea * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Scar * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Skin chapped * 1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Social circumstances       
Activities of daily living impaired * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Surgical and medical procedures       
Infection prophylaxis * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Medical device removal * 1  1/4 (25.00%)  1 0/4 (0.00%)  0 2/4 (50.00%)  2
Vascular disorders       
Haematoma * 1  0/4 (0.00%)  0 1/4 (25.00%)  2 1/4 (25.00%)  1
Hypertension * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Pallor * 1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
1
Term from vocabulary, MedDRA 13.1
*
Indicates events were collected by non-systematic assessment
The study was terminated as pre-specified efficacy criteria were not met. Data was not presented for efficacy parameters: ABR, Children's Sleep Habits Rating Scale, Infant Toddler QoL Questionnaire, SBRS.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Physician
Organization: Shire
Phone: 1 866-842-5335
EMail: ClinicalTransparency@shire.com
Layout table for additonal information
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01299727    
Other Study ID Numbers: HGT-SAN-067
2010-021348-16 ( EudraCT Number )
First Submitted: February 16, 2011
First Posted: February 18, 2011
Results First Submitted: March 12, 2020
Results First Posted: April 21, 2020
Last Update Posted: April 21, 2020