A safety, tolerability and preliminary efficacy study of idursulfase-IT in patients with Hunter syndrome associated with learning disability
- Conditions
- Treatment of Hunter syndrome and cognitive impairmentMedDRA version: 14.1 Level: PT Classification code 10056889 Term: Mucopolysaccharidosis II System Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Body processes [G] - Genetic Phenomena [G05]
- Registration Number
- EUCTR2010-020048-36-GB
- Lead Sponsor
- Shire HGT, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 16
Patients must meet all of the following criteria to be considered eligible for enrollment:
1a) The patient has a deficiency in iduronate-2-sulfatase enzyme activity of =10% of the lower limit of the normal range as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory)
AND
1b) The patient has a documented mutation in the iduronate-2-sulfatase gene
OR
The patient has a normal enzyme activity level of one other sulfatase as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory)
2) The patient is male and is =3 and <18 years of age
3) The patient has evidence at Screening of Hunter syndrome-related cognitive impairment, defined as
a) The patient has an IQ =77
OR
b) There is evidence of a change of =1 (15 IQ points) but =2 (30 IQ points) standard deviations decline from a previous protocol-defined neurodevelopmental assessment. The duration of protocol-defined neurologic involvement is at least 3 months but less than 36 months as documented in the patient’s medical history.
4) The patient has received and tolerated a minimum of 6 months of treatment with weekly intravenous idursulfase, and has received 80% of the total planned infusions within that time frame, including having received 100% of the planned infusions within 4 weeks immediately preceding the surgical implantation of the IDDD.
5) The patient must have sufficient auditory capacity, with or without hearing aids, to complete the required protocol testing, and be compliant with wearing the aid on scheduled testing days.
6) The patient, patient’s parent(s), or legally authorized guardian(s) must have voluntarily signed an Institutional Review Board / Independent Ethics Committee-approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient. The guardians’ consent and patient’s assent, as relevant, must be obtained.
Are the trial subjects under 18? yes
Number of subjects for this age range: 20
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Patients who meet any of the following criteria are not eligible for this study:
1) The patient has clinically significant non-Hunter syndrome-related CNS involvement which is judged by the Investigator to be likely to interfere with the accurate administration and interpretation of protocol assessments.
2) The patient’s IQ is = 78
3) The patient has a CNS shunt.
4) The patient has experienced infusion-related anaphylactoid event(s) or has evidence of consistent severe adverse events related to treatment with Elaprase which, in the Investigator’s opinion, may pose an unnecessary risk to the patient.
5) The patient has any known or suspected hypersensitivity to anesthesia or is thought to be at an unacceptably high risk for anesthesia due to compromised airways or other conditions.
6) The patient has a history of complications from previous lumbar punctures or technical challenges in conducting lumbar punctures such that the potential risks would exceed possible benefits for the patient.
7) The patient or patient’s family has a history of neuroleptic malignant syndrome, malignant hyperthermia, or other anesthesia-related concerns.
8) The patient has a history of poorly controlled seizure disorder.
9) The patient has a significant medical or psychiatric comorbidity(ies) that might affect study data or confound the integrity of study results.
10) The patient is currently receiving chronic psychotropic therapy (eg, neuroleptics, benzodiazepines, antidepressants, anticonvulsants, stimulants) which in the Investigator’s opinion would likely affect the neurocognitive assessments. Intermittent use of selected short half-life agents (benzodiazepine, sedatives, etc) may be permitted as long as there are 5 half-lives between last drug administered and study-related procedures including neurocognitive assessments.
11) The patient has received treatment with any investigational drug or device within the 30 days prior to study entry.
12) The patient has received a cord blood or bone marrow transplant at any time or has received blood product transfusions within 90 days prior to Screening.
13) The patient is unable to comply with the protocol, (eg, has significant hearing or vision impairment, a clinically relevant medical condition making implementation of the protocol difficult, unstable social situation, known clinically significant psychiatric/behavioral instability, is unable to return for safety evaluations, or is otherwise unlikely to complete the study), as determined by the Investigator.
14) The patient has skeletomuscular/spinal abnormalities or other contraindications for the surgical implantation of the IDDD.
15) The patient has an opening CSF pressure upon lumbar puncture that exceeds 30.0 cm H2O.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method