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Trial record 2 of 32 for:    "mucopolysaccharidosis type III"

A Study of Patients With Sanfilippo Syndrome Type A (MPS IIIA)

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ClinicalTrials.gov Identifier: NCT01047306
Recruitment Status : Completed
First Posted : January 12, 2010
Results First Posted : March 30, 2016
Last Update Posted : March 30, 2016
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Observational
Study Design Observational Model: Cohort;   Time Perspective: Prospective
Condition Sanfilippo Syndrome Type A
Intervention Other: assessment
Enrollment 25

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description Children ≥1 to < 6 years of age with Sanfilippo Syndrome Type A (mucopolysaccharidosis type IIIA; MPS IIIA) who were untreated with any investigational products (drugs and/or devices). Children ≥ 6 years of age with Sanfilippo Syndrome Type A (mucopolysaccharidosis type IIIA; MPS IIIA) who were untreated with any investigational products (drugs and/or devices).
Period Title: Overall Study
Started 19 6
Discontinued From the Study 3 0
Completed 16 6
Not Completed 3 0
Reason Not Completed
Withdrawal by Subject             2             0
Lost to Follow-up             1             0
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old Total
Hide Arm/Group Description Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices). Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices). Total of all reporting groups
Overall Number of Baseline Participants 19 6 25
Hide Baseline Analysis Population Description
A maximum of 25 patients with MPS IIIA will be enrolled in the study to provide at least 12 patients who complete the study. This number was not based on any statistical consideration, but is expected to be adequate to describe the natural progression of Sanfilippo A syndrome.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants 6 participants 25 participants
4.29  (1.996) 12.44  (4.500) 6.24  (4.452)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 6 participants 25 participants
Female
6
  31.6%
3
  50.0%
9
  36.0%
Male
13
  68.4%
3
  50.0%
16
  64.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 19 participants 6 participants 25 participants
19 6 25
1.Primary Outcome
Title Change From Baseline in Bayley Scales of Infant Development-III/Kaufman Assessment Battery for Children-II (BSID-III/KABC-II) Age-Equivalent Scores
Hide Description Children 1 year-42 months were assessed by the BSID­III; those >42 months and with a developmental age of >42 months by the Vineland Adaptive Behavior Scales­II (VABS­II) were evaluated with the KABC­II. For children >42 months, but <42 months in developmental age, and those unable to complete at least 3 cognitive KABC­II subtests, the BSID­III was used. The BSID­III is a series of measurements to assess the motor, language, and cognitive development of infants and toddlers and consists of a series of developmental play tasks. The KABC­II is an individually administered measure of processing/reasoning abilities. 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 BSID­III and KABC­II age­ equivalent scores were based on the cognitive domain and average non-verbal age-equivalent score, respectively.
Time Frame Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.
Arm/Group Title Children < 6 Years Children ≥ 6 Years
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Mean (Standard Deviation)
Unit of Measure: months
6 months, n=18,6 0.17  (2.093) 1.19  (3.289)
12 months, n=18,6 -1.72  (4.625) 1.39  (4.029)
End of Study, n=15,5 -1.80  (7.143) 2.95  (4.652)
2.Primary Outcome
Title Change From Baseline in BSID-III/KABC-II Developmental Quotient (DQ) Scores
Hide Description The determination of whether a patient received BSID­III was based on an algorithm that includes the patient's calendar age and VABS­II age ­equivalent score (See Outcome 1). The BSID­III is a series of measurements to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers and consists of a series of developmental play tasks. The KABC­II is an individually administered measure of processing and reasoning abilities. The DQ is a means to express a neurodevelopmental/cognitive delay. The DQ was computed as a ratio and expressed as a percentage using the age-equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range: 0, 100). The BSID­III DQ score is based on the cognitive domain. The DQ score for KABC­II is calculated from the average non­verbal age-equivalent score. A positive value indicates improvement in health and cognition.
Time Frame Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.
Arm/Group Title Children < 6 Years Children ≥ 6 Years
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Mean (Standard Deviation)
Unit of Measure: percentage of chronological age
6 months, n=18,6 -7.42  (6.153) -0.03  (1.960)
12 months, n=18,6 -15.69  (9.258) -1.66  (2.977)
End of Study, n=15,5 -26.09  (14.788) -2.94  (2.588)
3.Primary Outcome
Title Change From Baseline in Vineland Adaptive Behavior Scales-II (VABS-II) Age-equivalent Scores
Hide Description The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. It is an instrument that supports the diagnosis of intellectual and developmental disabilities in patients from birth to 90 years. This test measures the following 5 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other 4 domains). The mean age-equivalent score is obtained by averaging out the age-equivalent scores for the all the sub-domains except for Gross and Fine motor skills (range: 0, unbound). A positive value indicates improvement in health and cognition
Time Frame Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.
Arm/Group Title Children < 6 Years Children ≥ 6 Years
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Mean (Standard Deviation)
Unit of Measure: months
6 months, n=17,6 -0.92  (3.966) -1.11  (5.661)
12 months, n=18,6 -0.90  (8.170) -2.63  (4.847)
End of Study, n=16,6 -2.29  (8.321) -7.80  (15.834)
4.Primary Outcome
Title Change From Baseline in VABS-II Overall DQ Scores
Hide Description The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. It is an instrument that supports the diagnosis of intellectual and developmental disabilities in patients from birth to 90 years. This test measures the following 5 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other 4 domains). The DQ is a means to express a neurodevelopmental/cognitive delay. The DQ was computed as a ratio and expressed as a percentage using the age-equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range, 0, 100). The overall DQ score is calculated from the mean age-equivalent score obtained by averaging out the age-equivalent scores for the all the sub-domains except for Gross and Fine motor skills. A positive value indicates improvement in health and cognition.
Time Frame Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.
Arm/Group Title Children < 6 Years Children ≥ 6 Years
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Mean (Standard Deviation)
Unit of Measure: percentage of chronological age
6 months, n=17,6 -9.33  (8.632) -2.78  (5.971)
12 months, n=18,6 -12.88  (15.131) -5.12  (7.683)
End of Study, n=16,6 -23.81  (14.655) -9.70  (11.299)
5.Secondary Outcome
Title Change From Baseline Values in Gray Matter Volume Assessed by Brain Magnetic Resonance Imaging (MRI)
Hide Description Total brain cortical gray matter volume was determined by analysis of brain MRI. The analysis was performed using “Freesurfer” software, which provides completely automated parcellation of the brain cortex and subcortical structures. In some cases, manual adjustments were necessary in cases of intensity normalization failure, resulting in erroneous white matter segmentation. A negative value indicates that gray matter volume decreased.
Time Frame Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.
Arm/Group Title Children < 6 Years Children ≥ 6 Years
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Mean (Standard Deviation)
Unit of Measure: milliliters
6 months, n=17,6 -15.98  (21.860) 1.16  (14.790)
12 months, n=16,6 -41.40  (36.319) -11.68  (13.126)
End of Study, n=9,5 -80.29  (45.867) -22.41  (18.134)
6.Secondary Outcome
Title Change From Baseline in The Total Disability Score (TDS) of The Four Point Scoring System (FPSS)
Hide Description The FPSS is an MPS III-specific disability assessment that evaluates motor function, expressive language, and cognitive function on a 0- to 3- point scale and can be used for individuals of all ages. A score of 3 points is assigned for normal function, 2 points for beginning of regression, 1 point for severe level of regression, and 0 points for lost skills. The total disability score (TDS) is the average of the motor function, speech, and cognitive function scores (range: 0, 3). The scoring is based on the parent’s response to a detailed questionnaire that covers several aspects of the disease. A positive value indicates improvement in function.
Time Frame Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.
Arm/Group Title Children < 6 Years Children ≥ 6 Years
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Mean (Standard Deviation)
Unit of Measure: units on a scale
6 months, n=18,6 -0.18  (0.411) 0.10  (0.245)
12 months, n=18,6 -0.31  (0.512) 0.10  (0.245)
End of Study, n=15,5 -0.43  (0.448) 0.18  (0.164)
7.Secondary Outcome
Title Percent of Participants With an Abnormal Overall Test Result of Auditory Brainstem Response (ABR) at Baseline
Hide Description Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. An abnormal value was greater than 21 decibels hearing level (dBHL).
Time Frame Baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: percentage of participants
Right ear, n=11,5 57.9 50.0
Left ear, n=11,5 57.9 66.7
8.Secondary Outcome
Title Percent of Participants With an Abnormal Overall Test Result of Auditory Brainstem Response (ABR) at 6 Months
Hide Description Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. An abnormal value was greater than 21 decibels hearing level (dBHL).
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: percentage of participants
Right ear, n=18,6 94.7 66.7
Left ear, n=18,6 94.7 66.7
9.Secondary Outcome
Title Percent of Participants With an Abnormal Overall Test Result of Auditory Brainstem Response (ABR) at 12 Months
Hide Description Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. An abnormal value was greater than 21 decibels hearing level (dBHL).
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: percentage of participants
Right ear, n=17,6 89.5 66.7
Left ear, n=17,6 89.5 83.3
10.Secondary Outcome
Title Percent of Participants With an Abnormal Overall Test Result of Auditory Brainstem Response (ABR) at End of Study
Hide Description Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. An abnormal value was greater than 21 decibels hearing level (dBHL).
Time Frame End of Study (12 months assessment or early termination)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: percentage of participants
Right ear, n=15,5 73.7 66.7
Left ear, n=15,5 78.9 66.7
11.Secondary Outcome
Title Percent of Participants With Sensorineural Hearing Loss at Baseline, as Assessed by the Auditory Brainstem Response (ABR)
Hide Description Sensorineural hearing loss occurs from damage to the inner ear, the brain, or the nerve that runs from the ear to the brain (auditory nerve). Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound­evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I­V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.
Time Frame Baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: percentage of participants
Right ear, n=9,3 21.1 16.7
Left ear, n=9,4 21.1 16.7
12.Secondary Outcome
Title Percent of Participants With Sensorineural Hearing Loss at 6 Months, as Assessed by the Auditory Brainstem Response (ABR)
Hide Description Sensorineural hearing loss occurs from damage to the inner ear, the brain, or the nerve that runs from the ear to the brain (auditory nerve). Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound­evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I­V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: percentage of participants
Right ear, n=18,4 63.2 50.0
Left ear, n=18,4 57.9 50.0
13.Secondary Outcome
Title Percent of Participants With Sensorineural Hearing Loss at 12 Months, as Assessed by the Auditory Brainstem Response (ABR)
Hide Description Sensorineural hearing loss occurs from damage to the inner ear, the brain, or the nerve that runs from the ear to the brain (auditory nerve). Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound­evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I­V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: percentage of participants
Right ear, n=17,4 84.2 50.0
Left ear, n=17,5 89.5 50.0
14.Secondary Outcome
Title Percent of Participants With Sensorineural Hearing Loss at End of Study, as Assessed by the Auditory Brainstem Response (ABR)
Hide Description Sensorineural hearing loss occurs from damage to the inner ear, the brain, or the nerve that runs from the ear to the brain (auditory nerve). Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound­evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I­V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.
Time Frame End of Study (12 months assessment or early termination)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: percentage of participants
Right ear, n=14,4 68.4 66.7
Left ear, n=15,4 78.9 66.7
15.Secondary Outcome
Title Percent of Participants With Conductive Hearing Loss at Baseline, as Assessed by the Auditory Brainstem Response (ABR)
Hide Description Conductive hearing loss occurs when there is a problem conducting sound waves along the route through the outer ear, tympanic membrane, or middle ear. Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound­evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (number of neurons firing), latency (speed of transmission), interpeak latency (time between peaks), and interaural latency (difference in wave V latency between ears). The interpeak latency I­V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.
Time Frame Baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: percentage of participants
Right ear, n=9,3 10.5 0.0
Left ear, n=9,4 10.5 16.7
16.Secondary Outcome
Title Percent of Participants With Conductive Hearing Loss at 6 Months, as Assessed by the Auditory Brainstem Response (ABR)
Hide Description Conductive hearing loss occurs when there is a problem conducting sound waves along the route through the outer ear, tympanic membrane, or middle ear. Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound­evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (number of neurons firing), latency (speed of transmission), interpeak latency (time between peaks), and interaural latency (difference in wave V latency between ears). The interpeak latency I­V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: percentage of participants
Right ear, n=18,4 5.3 0.0
Left ear, n=18,4 5.3 0.0
17.Secondary Outcome
Title Percent of Participants With Conductive Hearing Loss at 12 Months, as Assessed by the Auditory Brainstem Response (ABR)
Hide Description Conductive hearing loss occurs when there is a problem conducting sound waves along the route through the outer ear, tympanic membrane, or middle ear. Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound­evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (number of neurons firing), latency (speed of transmission), interpeak latency (time between peaks), and interaural latency (difference in wave V latency between ears). The interpeak latency I­V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: percentage of participants
Right ear, n=17,4 0.0 0.0
Left ear, n=17,5 0.0 16.7
18.Secondary Outcome
Title Percent of Participants With Conductive Hearing Loss at End of Study, as Assessed by the Auditory Brainstem Response (ABR)
Hide Description Conductive hearing loss occurs when there is a problem conducting sound waves along the route through the outer ear, tympanic membrane, or middle ear. Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound­evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (number of neurons firing), latency (speed of transmission), interpeak latency (time between peaks), and interaural latency (difference in wave V latency between ears). The interpeak latency I­V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.
Time Frame End of Study (12 months assessment or early termination)
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Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: percentage of participants
Right ear, n=14,4 0.0 0.0
Left ear, n=15,4 0.0 0.0
19.Secondary Outcome
Title Number of Participants With Mild, Moderate, or Severe Hearing Loss at Baseline, as Assessed by The Auditory Brain Response (ABR)
Hide Description Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. Mild hearing loss: 21-40 decibels hearing level (dBHL), moderate hearing loss: 41-70 dBHL, severe hearing loss: 71-90 dBHL.
Time Frame Baseline
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Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: participants
Right ear, n=11,3 11 3
Left ear, n=11,4 11 4
20.Secondary Outcome
Title Number of Participants With Mild, Moderate, or Severe Hearing Loss at 6 Months, as Assessed by The Auditory Brain Response (ABR)
Hide Description Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. Mild hearing loss: 21-40 decibels hearing level (dBHL), moderate hearing loss: 41-70 dBHL, severe hearing loss: 71-90 dBHL.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: participants
Right ear, n=18,4 18 4
Left ear, n=18,4 18 4
21.Secondary Outcome
Title Number of Participants With Mild, Moderate, or Severe Hearing Loss at 12 Months, as Assessed by The Auditory Brain Response (ABR)
Hide Description Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. Mild hearing loss: 21-40 decibels hearing level (dBHL), moderate hearing loss: 41-70 dBHL, severe hearing loss: 71-90 dBHL.
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: participants
Right ear, n=17,4 17 4
Left ear, n=17,5 17 5
22.Secondary Outcome
Title Number of Participants With Mild, Moderate, or Severe Hearing Loss at End of Study, as Assessed by The Auditory Brain Response (ABR)
Hide Description Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. Mild hearing loss: 21-40 decibels hearing level (dBHL), moderate hearing loss: 41-70 dBHL, severe hearing loss: 71-90 dBHL.
Time Frame End of Study (12 months assessment or early termination)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: participants
Right ear, n=14,4 14 4
Left ear, n=15,4 15 4
23.Secondary Outcome
Title Percent of Participants With Profound Hearing Loss, as Assessed by the Auditory Brainstem Response (ABR)
Hide Description Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. Profound hearing loss: 91+ decibels hearing level (dBHL).
Time Frame Baseline, 6 months, 12 months, End of Study (Month 24 assessment or early termination)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: percentage of participants
Baseline, n=11,3 0.0 0.0
6 months, n=18,4 0.0 0.0
12 months, n=17,4 0.0 0.0
End of Study, n=14,4 0.0 0.0
24.Secondary Outcome
Title Number of Participants With "Somewhat" or "Much" Worse Change in Health as Assessed by The Child Health Questionnaire Parent Form 50 (CHQ-PF50)
Hide Description The parent form, CHQ-PF50, is designed to measure the physical and psychosocial well-being of children 5 years and older. In this trial it was used to assess the health of children 5 to 18 years of age. It consists of 13 health concepts including 11 multi-item and 2 single-item scales: physical function, role/social-emotional/behavioral, role/social-physical, bodily pain, general behavior, mental health, self-esteem, general health perceptions, change in health, parental impact-emotional, parental impact-time, family activities, and family cohesion. The parental impact scales capture the amount of emotional distress and time limitation experienced by the parent due to the child’s physical health, emotional well-being, attention/learning abilities, ability to get along with others, and general behavior. The Change in Health section assesses changes in health over the previous year.
Time Frame Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
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Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: participants
Baseline, n=6,4 1 2
6 months, n=3,5 1 1
12 months, n=7,5 3 1
End of Study, n=11,6 2 3
25.Secondary Outcome
Title Change From Baseline in The Infant Toddler Quality of Life Questionnaire (ITQoL) Growth And Development Subscale
Hide Description The ITQoL Questionnaire is a generic, validated health status measure for children aged 2 months up to 5 years, including items and scales to measure aspects of physical functioning, development, pain, mood, behavior, general health, and impact on parents. In this study the ITQoL was also administered to patients who were developmentally functioning at or below the age of years. Growth and development is one of 12 health concepts measured by ITQoL. Transformed scores for all subscales range from 0 to 100, with a higher score indicating better health. A positive value indicates improvement.
Time Frame Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
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Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Mean (Standard Deviation)
Unit of Measure: units on a scale
6 months, n=10 -8.50  (12.813) NA [1]   (NA)
12 months, n=9 -20.56  (16.853) NA [1]   (NA)
End of Study, n=4 -28.13  (13.901) NA [1]   (NA)
[1]
This scale is not used with children in this age group.
26.Secondary Outcome
Title Change From Baseline in The Total Sleep Disturbance (TSD) Score of The Children’s Sleep Habits Questionnaire (CSHQ)
Hide Description The CSHQ is a validated, retrospective, parent-reported sleep screening tool. The questionnaire consists of 35 items that yield a TSD score, as well as 8 subscale scores, including bedtime resistance, sleep duration, parasomnias, sleep disordered breathing, night wakings, daytime sleepiness, sleep anxiety, and sleep onset delay. The questionnaire was designed for children aged 4 to 12 years. Parents were asked to think of a recent “typical” week of their child’s sleep and to indicate how often sleep disturbance behaviors occurred. A 3-point scale was used for rating: “usually” if the sleep behavior occurs 5 to 7 times per week, “sometimes” for 2 to 4 times per week, and “rarely” for once or not at all during the week. The TSD score, which is the sum of all responses, included all items of the 8 subscales, but consisted of only 33 items because two on the bedtime resistance and sleep anxiety subscales were identical (range: 0, 99). A negative value indicates less sleep disturbance.
Time Frame Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Mean (Standard Deviation)
Unit of Measure: units on a scale
6 months, n=8,3 1.75  (9.968) 3.33  (8.145)
12 months, n=8,3 -0.13  (9.862) -2.00  (1.732)
End of Study, n=7,3 0.86  (16.098) 0.33  (6.028)
27.Other Pre-specified Outcome
Title Change From Baseline in Urine Glycosaminoglycan (GAG) Levels
Hide Description Urine GAG was measured by a dye binding assay. A negative value indicates that GAG levels decreased.
Time Frame Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.
Arm/Group Title Children < 6 Years Children ≥ 6 Years
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Mean (Standard Deviation)
Unit of Measure: mg GAG/mmol creatinine
6 months, n=18,6 0.26  (19.379) -10.23  (32.983)
12 months, n=18,6 -0.39  (19.429) -7.95  (31.516)
End of Study, n=15,5 -0.33  (22.706) -6.34  (28.810)
28.Other Pre-specified Outcome
Title Change From Baseline in Total Tau Levels in Cerebrospinal Fluid (CSF)
Hide Description Tau proteins are involved in the building and stabilization of axonal microtubules in the CNS. The phosphorylation of tau proteins associated with microtubules is believed to be involved in destabilizing axons and extensively phosphorylated tau (ptau) has been observed in patients with Alzheimer disease and other neurodegenerative diseases. Because MPS IIIA is a neurodegenerative disease, CSF tau levels were determined to evaluate the potential role of this process in the natural history of the disease. A negative value indicates that total tau levels decreased.
Time Frame Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
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Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.
Arm/Group Title Children < 6 Years Children ≥ 6 Years
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Mean (Standard Deviation)
Unit of Measure: picograms/milliliter
6 months, n=17,6 -88.9  (236.58) 54.8  (177.63)
12 months, n=18,6 -95.8  (375.45) -79.8  (96.01)
End of Study, n=14,5 -80.9  (562.50) -133.2  (141.82)
29.Other Pre-specified Outcome
Title Change From Baseline in Phosphorylated Tau Levels in Cerebrospinal Fluid (CSF)
Hide Description Tau proteins are involved in the building and stabilization of axonal microtubules in the CNS. The phosphorylation of tau proteins associated with microtubules is believed to be involved in destabilizing axons and extensively phosphorylated tau (ptau) has been observed in patients with Alzheimer disease and other neurodegenerative diseases. Because MPS IIIA is a neurodegenerative disease, CSF phosphorylated tau levels were determined to evaluate the potential role of this process in the natural history of the disease. A negative value indicates that phosphorylated tau levels decreased.
Time Frame Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.
Arm/Group Title Children < 6 Years Children ≥ 6 Years
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Mean (Standard Deviation)
Unit of Measure: picograms/milliliter
6 months, n=17,5 -5.42  (20.722) -1.56  (6.518)
12 months, n=18,5 -15.04  (25.550) -5.42  (5.508)
End of Study, n=14,4 -29.98  (41.190) -29.45  (9.963)
30.Post-Hoc Outcome
Title Percent of Participants With Thickened Heart Valves as Assessed by Echocardiography (ECG)
Hide Description ECG allows a non-invasive assessment of cardiac structure, function, and hemodynamics and can provide essential insight into mechanisms of disease and therapeutic benefit.
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: percentage of participants
Tricuspid Valve, n=18,6 5.3 0.0
Pulmonary Valve, n=18,6 0.0 0.0
Mitral Valve, n=18,6 57.9 66.7
Aortic Valve, n=18,6 15.8 16.7
31.Post-Hoc Outcome
Title Percent of Participants With Trace Regurgitation as Assessed by ECG
Hide Description ECG allows a non-invasive assessment of cardiac structure, function, and hemodynamics and can provide essential insight into mechanisms of disease and therapeutic benefit. Regurgitation indicates that blood flows backwards through the valve.
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Measure Type: Number
Unit of Measure: percentage of participants
Tricuspid Valve, n=18,6 73.7 100.0
Pulmonary Valve, n=16,5 63.2 66.7
Mitral Valve, n=18,6 36.8 16.7
Aortic Valve, n=18,6 21.1 0.0
32.Post-Hoc Outcome
Title Change From Baseline in Tricuspid Valve Regurgitant Velocity
Hide Description ECG allows a non-invasive assessment of cardiac structure, function, and hemodynamics and can provide essential insight into mechanisms of disease and therapeutic benefit. Backwards blood flow through the tricuspid valve is measured during one heartbeat. A negative value indicates decreased velocity.
Time Frame Baseline, 6 months, 12 months, End of Study (Month 24 assessment or early termination)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Mean (Standard Deviation)
Unit of Measure: meters/second
6 months, n=2,1 -0.325  (0.106) 1.990  (0.0)
12 months, n=4,2 -0.013  (0.210) 1.210  (1.428)
End of Study, n=3,1 -0.087  (0.078) 2.030  (0.0)
33.Post-Hoc Outcome
Title Change From Baseline in The Ratio of Mitral Valve Early Inflow Velocity (E) to Late Inflow Velocity (A)
Hide Description ECG allows a non-invasive assessment of cardiac structure, function, and hemodynamics and can provide essential insight into mechanisms of disease and therapeutic benefit. Blood flow through the mitral valve is measured during one heartbeat.The E/A ratio measures the relationship between early (E) and late (A) inflow velocity by dividing E by A. A positive value indicates that either early flow through the mitral valve (E) increased or late flow through the valve (A) decreased.
Time Frame Baseline, 6 months, 12 months, End of Study (Month 24 assessment or early termination)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Mean (Standard Deviation)
Unit of Measure: quotient of E/A
6 months, n=4,1 0.196  (0.418) 0.059  (0.0)
12 months, n=3,1 0.293  (0.404) -0.608  (0.0)
End of Study, n=4,2 -0.081  (0.529) -0.226  (0.096)
34.Post-Hoc Outcome
Title Change From Baseline in Liver Volume as Assessed by Abdominal Magnetic Resonance Imaging (MRI)
Hide Description Liver volume was obtained via abdominal MRI. A negative value indicates that volume decreased.
Time Frame Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Mean (Standard Deviation)
Unit of Measure: milliliters
6 months, n=5,2 93.00  (237.960) 190.00  (91.924)
12 months, n=5,2 39.20  (248.532) 280.00  (32.527)
End of Study, n=4,2 356.00  (197.985) 188.50  (41.719)
35.Post-Hoc Outcome
Title Change From Baseline in Spleen Volume as Assessed by Abdominal Magnetic Resonance Imaging (MRI)
Hide Description Spleen volume was assessed via abdominal MRI. A negative value indicates that volume decreased.
Time Frame Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.
Arm/Group Title Children < 6 Years Old Children ≥ 6 Years Old
Hide Arm/Group Description:
Children ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Children ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
Overall Number of Participants Analyzed 19 6
Mean (Standard Deviation)
Unit of Measure: milliliters
6 months, n=5,2 29.60  (63.552) 11.50  (0.707)
12 months, n=5,2 238.40  (473.682) 44.00  (2.828)
End of Study, n=4,2 128.50  (71.276) 13.00  (28.284)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Children < 6 Years Children ≥ 6 Years
Hide Arm/Group Description Patients ≥1 to < 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices). Patients ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).
All-Cause Mortality
Children < 6 Years Children ≥ 6 Years
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Children < 6 Years Children ≥ 6 Years
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/19 (0.00%)      0/6 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Children < 6 Years Children ≥ 6 Years
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/19 (42.11%)      3/6 (50.00%)    
Ear and labyrinth disorders     
Ear Haemorrhage  1  0/19 (0.00%)  0 1/6 (16.67%)  1
Gastrointestinal disorders     
Vomiting  1  6/19 (31.58%)  6 1/6 (16.67%)  1
General disorders     
Chills  1  1/19 (5.26%)  1 0/6 (0.00%)  0
Pain  1  1/19 (5.26%)  1 0/6 (0.00%)  0
Pyrexia  1  1/19 (5.26%)  1 0/6 (0.00%)  0
Injury, poisoning and procedural complications     
Procedural nausea  1  2/19 (10.53%)  2 0/6 (0.00%)  0
Post Lumbar Puncture Syndrome  1  0/19 (0.00%)  0 1/6 (16.67%)  1
Procedural Headache  1  1/19 (5.26%)  1 0/6 (0.00%)  0
Procedural Vomiting  1  1/19 (5.26%)  1 0/6 (0.00%)  0
Nervous system disorders     
Headache  1  1/19 (5.26%)  1 0/6 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Laryngospasm  1  1/19 (5.26%)  1 0/6 (0.00%)  0
Wheezing  1  1/19 (5.26%)  1 0/6 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.1)
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.
Shire's agreements with investigators vary. All agreements provide Shire the right to embargo communications regarding trial results prior to public release for a period ≤180 days from the time submitted to Shire for review. Shire does not prohibit publication, but can require the removal of confidential information (excluding trial results) and can request postponement of a single-center publication until after disclosure of the trial's multi-center publication.
Results Point of Contact
Name/Title: Study Physician
Organization: Shire Development LLC
Phone: +1 866 842 5335
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01047306     History of Changes
Other Study ID Numbers: HGT-SAN-053
First Submitted: January 11, 2010
First Posted: January 12, 2010
Results First Submitted: February 9, 2015
Results First Posted: March 30, 2016
Last Update Posted: March 30, 2016