A Safety and Dose Ranging Study of Idursulfase (Intrathecal) Administration Via an Intrathecal Drug Delivery Device in Pediatric Patients With Hunter Syndrome Who Have Central Nervous System Involvement and Are Receiving Treatment With Elaprase®

• Register: ClinicalTrials.gov
• Last refreshed on: 5 July 2021
• Main ID: NCT00920647
• Date of registration: 12/06/2009
• Prospective Registration: Yes
• Primary sponsor: Shire
• Public title: A Safety and Dose Ranging Study of Idursulfase (Intrathecal) Administration Via an Intrathecal Drug Delivery Device in Pediatric Patients With Hunter Syndrome Who Have Central Nervous System Involvement and Are Receiving Treatment With Elaprase®
• Scientific title: A Phase I/II, Randomized, Safety and Ascending Dose Ranging Study of Intrathecal Idursulfase-IT Administered in Conjunction With Intravenous Elaprase in Pediatric Patients With Hunter Syndrome and Cognitive Impairment
• Date of first enrolment: November 18, 2009
• Target sample size: 16
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00920647
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United Kingdom, United States

Contacts

• Name: Study Director
• Affiliation: Takeda

Key inclusion & exclusion criteria

Inclusion Criteria:

1a. 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. A documented mutation in the iduronate-2-sulfatase gene OR 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 early stage (duration and severity metrics per
protocol) Hunter syndrome-related Central Nervous System (CNS) involvement, defined as:

- The patient has an Intelligence quotient (IQ) =77 OR

- There is evidence of a change of =1 but =2 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 insertion of the IDDD.

5. The patient must have sufficient auditory capacity, with or without 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 must be
obtained.

Exclusion Criteria:

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 has an IQ =78

3. The patient has a CNS shunt.

4. The patient has experienced an infusion-related anaphylactoid event 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 (e.g., neuroleptics,
benzodiazepines, antidepressants, anticonvulsants, stimulants, etc.) 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, (e.g., 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 cm
H2O(water) .



Age minimum: 3 Years
Age maximum: 18 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Hunter Syndrome

Intervention(s)

Drug: Idursulfase IT (10 mg)

Drug: Idursulfase IT (30 mg)

Other: Control

Drug: Idursulfase IT (1 mg)

Primary Outcome(s)

Safety: Development of Anti-idursulfase Antibodies (Serum) [Time Frame: 6 months]

Clinically Significant ECG Findings at Any Time During the Study. [Time Frame: 6 months]

Number of Serious Adverse Event (SAE) [Time Frame: 6 months]

Safety Changes in Cerebrospinal Fluid (CSF)- White Blood Cells (WBC) [Time Frame: 6 months]

Number of Treatment Emergent Adverse Event (AE) [Time Frame: Baseline to week 23]

Safety: Development of Anti-idursulfase Antibodies (CSF) [Time Frame: 6 months]

Secondary Outcome(s)

Change From Baseline in CSF Glycosaminoglycans [GAGs] at Week 27 [Time Frame: Baseline to Week 27]

Level of Idursulfase in the CSF Compartment Resulting From Monthly Idursulfase IT Administrations [Time Frame: Week 27 (end of study)]

% Change From Baseline in Urinary GAG [Time Frame: Baseline to Week 27]

Concentration of Idursulfase in Serum After Repeated Doses of Intrathecal Idursulfase-IT Given in Conjunction With Elaprase [Time Frame: Weeks 23]

Concentration of Idursulfase in Serum After Single Administration (Week 3) in Conjunction With Elaprase [Time Frame: Weeks 3]

Secondary ID(s)

2010-020048-36

HGT-HIT-045

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 16/05/2014
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00920647