Clinical trial NCT01047306: A Study of Patients With Sanfilippo Syndrome Type A (MPS IIIA)
Official title: A Longitudinal, Prospective, Natural History Study of Patients With Sanfilippo Syndrome Type A (MPS IIIA)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sanfilippo Syndrome Type A
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-01-12
Enrollment: 25
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Initial patient eligibility is based on patient age and on a confirmed diagnosis of MPS IIIA by biochemical enzyme assay.

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.


Eligibility criteria: Inclusion Criteria:

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).

AND

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.

3. Patient is medically stable to accommodate the protocol requirements, including travel and assessments, without placing an undue burden on the patient/patient's family.

4. 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.

Exclusion Criteria:

1. 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.
2. Patients who, for MPS IIIA behavioral-related reasons,in the opinion of the investigator, would preclude performance of study neurocognitive and developmental testing procedures.
3. 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.
4. Patient is blind and/or deaf.
5. Patient has any known or suspected hypersensitivity to anesthesia or is thought to be at an unacceptably high risk for anesthesia due to airway compromise or other conditions.
6. Patient or patient family history of neuroleptic malignant syndrome, malignant hyperthermia, or other anesthesia-related concerns.
7. The Investigator may choose to exclude patients who have had complications resulting from prior lumbar punctures.
8. Patient history of poorly controlled seizure disorder.
9. 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.
10. Patient is currently receiving psychotropic or other medications which in the investigator's opinion, would be likely to substantially confound test results.
11. 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.
12. 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).
13. Patient has received a hematopoietic stem cell or bone marrow transplant.
14. 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.
15. 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.

Primary outcomes:
measure: Change From Baseline in Bayley Scales of Infant Development-III/Kaufman Assessment Battery for Children-II (BSID-III/KABC-II) Age-Equivalent Scores
timeFrame: Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
measure: Change From Baseline in BSID-III/KABC-II Developmental Quotient (DQ) Scores
timeFrame: Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
measure: Change From Baseline in Vineland Adaptive Behavior Scales-II (VABS-II) Age-equivalent Scores
timeFrame: Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
measure: Change From Baseline in VABS-II Overall DQ Scores
timeFrame: Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
Secondary outcomes:
measure: Change From Baseline Values in Gray Matter Volume Assessed by Brain Magnetic Resonance Imaging (MRI)
timeFrame: Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
measure: Change From Baseline in The Total Disability Score (TDS) of The Four Point Scoring System (FPSS)
timeFrame: Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
measure: Percent of Participants With an Abnormal Overall Test Result of Auditory Brainstem Response (ABR) at Baseline
timeFrame: Baseline
measure: Percent of Participants With an Abnormal Overall Test Result of Auditory Brainstem Response (ABR) at 6 Months
timeFrame: 6 months
measure: Percent of Participants With an Abnormal Overall Test Result of Auditory Brainstem Response (ABR) at 12 Months
timeFrame: 12 months
measure: Percent of Participants With an Abnormal Overall Test Result of Auditory Brainstem Response (ABR) at End of Study
timeFrame: End of Study (12 months assessment or early termination)
measure: Percent of Participants With Sensorineural Hearing Loss at Baseline, as Assessed by the Auditory Brainstem Response (ABR)
timeFrame: Baseline
measure: Percent of Participants With Sensorineural Hearing Loss at 6 Months, as Assessed by the Auditory Brainstem Response (ABR)
timeFrame: 6 months
measure: Percent of Participants With Sensorineural Hearing Loss at 12 Months, as Assessed by the Auditory Brainstem Response (ABR)
timeFrame: 12 months
measure: Percent of Participants With Sensorineural Hearing Loss at End of Study, as Assessed by the Auditory Brainstem Response (ABR)
timeFrame: End of Study (12 months assessment or early termination)
measure: Percent of Participants With Conductive Hearing Loss at Baseline, as Assessed by the Auditory Brainstem Response (ABR)
timeFrame: Baseline
measure: Percent of Participants With Conductive Hearing Loss at 6 Months, as Assessed by the Auditory Brainstem Response (ABR)
timeFrame: 6 months
measure: Percent of Participants With Conductive Hearing Loss at 12 Months, as Assessed by the Auditory Brainstem Response (ABR)
timeFrame: 12 months
measure: Percent of Participants With Conductive Hearing Loss at End of Study, as Assessed by the Auditory Brainstem Response (ABR)
timeFrame: End of Study (12 months assessment or early termination)
measure: Number of Participants With Mild, Moderate, or Severe Hearing Loss at Baseline, as Assessed by The Auditory Brain Response (ABR)
timeFrame: Baseline
measure: Number of Participants With Mild, Moderate, or Severe Hearing Loss at 6 Months, as Assessed by The Auditory Brain Response (ABR)
timeFrame: 6 months
measure: Number of Participants With Mild, Moderate, or Severe Hearing Loss at 12 Months, as Assessed by The Auditory Brain Response (ABR)
timeFrame: 12 months
measure: Number of Participants With Mild, Moderate, or Severe Hearing Loss at End of Study, as Assessed by The Auditory Brain Response (ABR)
timeFrame: End of Study (12 months assessment or early termination)
measure: Percent of Participants With Profound Hearing Loss, as Assessed by the Auditory Brainstem Response (ABR)
timeFrame: Baseline, 6 months, 12 months, End of Study (Month 24 assessment or early termination)
measure: Number of Participants With "Somewhat" or "Much" Worse Change in Health as Assessed by The Child Health Questionnaire Parent Form 50 (CHQ-PF50)
timeFrame: Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
measure: Change From Baseline in The Infant Toddler Quality of Life Questionnaire (ITQoL) Growth And Development Subscale
timeFrame: Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
measure: Change From Baseline in The Total Sleep Disturbance (TSD) Score of The Children's Sleep Habits Questionnaire (CSHQ)
timeFrame: Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
Other outcomes:
measure: Change From Baseline in Urine Glycosaminoglycan (GAG) Levels
timeFrame: Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
measure: Change From Baseline in Total Tau Levels in Cerebrospinal Fluid (CSF)
timeFrame: Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
measure: Change From Baseline in Phosphorylated Tau Levels in Cerebrospinal Fluid (CSF)
timeFrame: Baseline, 6 months, 12 months, and End of Study (Month 24 assessment or early termination)
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Cingi EC, Beebe DS, Whitley CB, Belani KG. Anesthetic care and perioperative complications in children with Sanfilipo Syndrome Type A. Paediatr Anaesth. 2016 May;26(5):531-8. doi: 10.1111/pan.12876. Epub 2016 Mar 9.
citation: Shapiro EG, Nestrasil I, Delaney KA, Rudser K, Kovac V, Nair N, Richard CW 3rd, Haslett P, Whitley CB. A Prospective Natural History Study of Mucopolysaccharidosis Type IIIA. J Pediatr. 2016 Mar;170:278-87.e1-4. doi: 10.1016/j.jpeds.2015.11.079. Epub 2016 Jan 16.
citation: Shapiro EG, Nestrasil I, Ahmed A, Wey A, Rudser KR, Delaney KA, Rumsey RK, Haslett PA, Whitley CB, Potegal M. Quantifying behaviors of children with Sanfilippo syndrome: the Sanfilippo Behavior Rating Scale. Mol Genet Metab. 2015 Apr;114(4):594-8. doi: 10.1016/j.ymgme.2015.02.008. Epub 2015 Mar 5.
citation: Rumsey RK, Rudser K, Delaney K, Potegal M, Whitley CB, Shapiro E. Acquired autistic behaviors in children with mucopolysaccharidosis type IIIA. J Pediatr. 2014 May;164(5):1147-1151.e1. doi: 10.1016/j.jpeds.2014.01.007. Epub 2014 Feb 25.