A Longitudinal, Prospective, Natural History Study of Patients With Sanfilippo Syndrome Type A (MPS IIIA)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Change From Baseline in BSID-III/KABC-II Developmental Quotient (DQ) Scores
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Year 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1a. Documented deficiency in HNS enzyme activity of less than or equal to 10% of the lower limit of the normal range as measured in fibroblasts or leukocytes (based on normal range for diagnosis of MPS IIIA by a laboratory that is acceptable to Shire HGT).
- •1b. Normal enzyme activity level of at least one other sulfatase (to rule out multiple sulfatase deficiency) as measured in fibroblasts or leukocytes (based on normal range by a laboratory that is acceptable to Shire HGT).
- •2.Patient is greater than or equal to 1 year of age and developmental age greater than or equal to 1 year.
- •Patient is medically stable to accommodate the protocol requirements, including travel and assessments, without placing an undue burden on the patient/patient's family.
- •Voluntarily signed an IRB/IEC-approved informed consent (assent if applicable) form. The patient's, patient's parents or legally authorized representative(s) consent and patient's assent as appropriate, must be obtained.
排除标准
- •Patient has significant non-MPS IIIA-related CNS impairment or behavioral disturbances, which would confound the scientific integrity or interpretation of study assessments, as determined by the investigator.
- •Patients who, for MPS IIIA behavioral-related reasons,in the opinion of the investigator, would preclude performance of study neurocognitive and developmental testing procedures.
- •Patients who are pregnant, breast feeding, or female patients of childbearing potential, who will not or cannot comply with the use of an acceptable method of birth control such as condoms, barrier method, oral contraception, etc.
- •Patient is blind and/or deaf.
- •Patient has any known or suspected hypersensitivity to anesthesia or is thought to be at an unacceptably high risk for anesthesia due to airway compromise or other conditions.
- •Patient or patient family history of neuroleptic malignant syndrome, malignant hyperthermia, or other anesthesia-related concerns.
- •The Investigator may choose to exclude patients who have had complications resulting from prior lumbar punctures.
- •Patient history of poorly controlled seizure disorder.
- •Patient history of an intracranial pressure (ICP) or opening CSF pressure upon lumbar puncture that exceeds 30 cm water that has not been definitively treated.
- •Patient is currently receiving psychotropic or other medications which in the investigator's opinion, would be likely to substantially confound test results.
- •Patient cannot sustain absence from aspirin, non-steroidals, or medications that affect blood clotting within 1 week prior to a relevant study related procedure (eg, lumbar puncture if applicable), or has ingested such medications within 1 week before any procedures in which any change in clotting activity would be deleterious.
- •Patient has received treatment with any investigational drug or device intended as a treatment for MPS IIIA within the 30 days prior to, or during the study, or is currently enrolled in another study that involves an investigational drug or device (enrollment through Safety follow-up contact).
- •Patient has received a hematopoietic stem cell or bone marrow transplant.
- •Patient's assent is unattainable, or the patient's parent(s), or patient's legally authorized representative(s) is/are unable to understand the nature, scope, and possible consequences of the study, or do/does not agree to comply with the protocol defined schedule of assessments.
- •The patient has any item (braces, tattoos, etc.) which would exclude the patient from being able to undergo MRI according to local Institutional Policy, or the patient has any other situation that would exclude the patient from undergoing any other procedure required in this study.
结局指标
主要结局
Change From Baseline in BSID-III/KABC-II Developmental Quotient (DQ) Scores
时间窗: 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 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 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 BSID-III DQ score is based on the cognitive domain. The DQ score for KABC-II is calculated from the average non-verbal age-equivalent score. A positive value indicates improvement in health and cognition.
Change From Baseline in Vineland Adaptive Behavior Scales-II (VABS-II) Age-equivalent Scores
时间窗: Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
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
Change From Baseline in VABS-II Overall DQ Scores
时间窗: Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
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.
Change From Baseline in Bayley Scales of Infant Development-III/Kaufman Assessment Battery for Children-II (BSID-III/KABC-II) Age-Equivalent Scores
时间窗: 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.
次要结局
- Change From Baseline in The Total Disability Score (TDS) of The Four Point Scoring System (FPSS)(Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination))
- Percent of Participants With Conductive Hearing Loss at 6 Months, as Assessed by the Auditory Brainstem Response (ABR)(6 months)
- Percent of Participants With Sensorineural Hearing Loss at Baseline, as Assessed by the Auditory Brainstem Response (ABR)(Baseline)
- Percent of Participants With Sensorineural Hearing Loss at 12 Months, as Assessed by the Auditory Brainstem Response (ABR)(12 months)
- Percent of Participants With Conductive Hearing Loss at Baseline, as Assessed by the Auditory Brainstem Response (ABR)(Baseline)
- Percent of Participants With an Abnormal Overall Test Result of Auditory Brainstem Response (ABR) at 12 Months(12 months)
- Percent of Participants With Sensorineural Hearing Loss at End of Study, as Assessed by the Auditory Brainstem Response (ABR)(End of Study (12 months assessment or early termination))
- Change From Baseline Values in Gray Matter Volume Assessed by Brain Magnetic Resonance Imaging (MRI)(Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination))
- Percent of Participants With an Abnormal Overall Test Result of Auditory Brainstem Response (ABR) at End of Study(End of Study (12 months assessment or early termination))
- Number of Participants With Mild, Moderate, or Severe Hearing Loss at 12 Months, as Assessed by The Auditory Brain Response (ABR)(12 months)
- Percent of Participants With an Abnormal Overall Test Result of Auditory Brainstem Response (ABR) at Baseline(Baseline)
- Percent of Participants With an Abnormal Overall Test Result of Auditory Brainstem Response (ABR) at 6 Months(6 months)
- Percent of Participants With Sensorineural Hearing Loss at 6 Months, as Assessed by the Auditory Brainstem Response (ABR)(6 months)
- Percent of Participants With Conductive Hearing Loss at 12 Months, as Assessed by the Auditory Brainstem Response (ABR)(12 months)
- Change From Baseline in The Infant Toddler Quality of Life Questionnaire (ITQoL) Growth And Development Subscale(Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination))
- Percent of Participants With Conductive Hearing Loss at End of Study, as Assessed by the Auditory Brainstem Response (ABR)(End of Study (12 months assessment or early termination))
- Number of Participants With Mild, Moderate, or Severe Hearing Loss at Baseline, as Assessed by The Auditory Brain Response (ABR)(Baseline)
- Number of Participants With Mild, Moderate, or Severe Hearing Loss at 6 Months, as Assessed by The Auditory Brain Response (ABR)(6 months)
- Change From Baseline in The Total Sleep Disturbance (TSD) Score of The Children's Sleep Habits Questionnaire (CSHQ)(Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination))
- Number of Participants With Mild, Moderate, or Severe Hearing Loss at End of Study, as Assessed by The Auditory Brain Response (ABR)(End of Study (12 months assessment or early termination))
- Number of Participants With "Somewhat" or "Much" Worse Change in Health as Assessed by The Child Health Questionnaire Parent Form 50 (CHQ-PF50)(Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination))
- Percent of Participants With Profound Hearing Loss, as Assessed by the Auditory Brainstem Response (ABR)(Baseline, 6 months, 12 months, End of Study (Month 24 assessment or early termination))