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

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: A Longitudinal, Prospective, Natural History Study of Patients With Sanfilippo Syndrome Type A (MPS IIIA)

Brief Summary: The purpose is to evaluate the course of disease progression in MPS IIIA patients who are untreated to identify potential surrogate endpoints that may be utilized in future ERT trials of MPS IIIA via defined assessments including standardized clinical, biochemical, neurocognitive, behavioral, developmental, and imaging measures.

Detailed Summary:
Sponsor: Shire

Current Primary Outcome:

  • Change From Baseline in Bayley Scales of Infant Development-III/Kaufman Assessment Battery for Children-II (BSID-III/KABC-II) Age-Equivalent Scores [ Time Frame: Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination) ]
    Children 1 year-42 months were assessed by the BSID-III; those >42 months and with a developmental age of >42 months by the Vineland Adaptive Behavior Scales-II (VABS-II) were evaluated with the KABC-II. For children >42 months, but <42 months in developmental age, and those unable to complete at least 3 cognitive KABC-II subtests, the BSID-III was used. The BSID-III 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 KABC-II 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 BSID-III and KABC-II age- equivalent scores were based on the cognitive domain and average non-verbal age-equivalent score, respectively.
  • Change From Baseline in BSID-III/KABC-II Developmental Quotient (DQ) Scores [ Time Frame: Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination) ]
    The determination of whether a patient received BSID-III was based on an algorithm that includes the patient's calendar age and VABS-II age -equivalent score (See Outcome 1). The BSID-III is a series of measurements to assess the motor (fine and gross), language (receptive and expressive), and co

    Original Primary Outcome: To evaluate the course of disease progression in patients with MPS IIIA who are untreated with any investigational products to inform possible future treatment studies [ Time Frame: 13 months ]

    Current Secondary Outcome:

    • Change From Baseline Values in Gray Matter Volume Assessed by Brain Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination) ]
      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.
    • Change From Baseline in The Total Disability Score (TDS) of The Four Point Scoring System (FPSS) [ Time Frame: Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination) ]
      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.
    • Percent of Participants With an Abnormal Overall Test Result of Auditory Brainstem Response (ABR) at Baseline [ Time Frame: Baseline ]
      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).
    • Percent of Participants With an Abnormal Overall Test Result of Auditory Brainstem Response (ABR) at 6 Months [ Time Frame: 6 months ]
      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).
    • Percent of Participants With an Abnormal Overall Test Result of Auditory Brainstem Response (ABR) at 12 Months [ Time Frame: 12 months ]
      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).
    • Percent of Participants With an Abnormal Overall Test Result of Auditory Brainstem Response (ABR) at End of Study [ Time Frame: End of Study (12 months assessment or early termination) ]
      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 int

      Original Secondary Outcome:

      Information By: Shire

      Dates:
      Date Received: January 11, 2010
      Date Started: February 2010
      Date Completion:
      Last Updated: February 29, 2016
      Last Verified: February 2016