Trial from ClinicalTrials.gov

For full trial details, please see the original record at



Trial ID
NCT02055118
Ethics application status
Date submitted
17/01/2014
Date registered
17/01/2014
Date last updated
28/03/2017

Titles & IDs
Public title
Study of Intrathecal Idursulfase-IT Administered in Conjunction With Elaprase® in Pediatric Patients With Hunter Syndrome and Early Cognitive Impairment
Scientific title
A Controlled, Randomized, Two-arm, Open-label, Assessor-blinded, Multicenter Study of Intrathecal Idursulfase-IT Administered in Conjunction With Elaprase® in Pediatric Patients With Hunter Syndrome and Early Cognitive Impairment
Secondary ID [1] 0 0
2013-002885-38
Secondary ID [2] 0 0
HGT-HIT-094
Universal Trial Number (UTN)
Trial acronym
AIM-IT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hunter Syndrome 0 0
Condition category
Condition code
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above
Mental Health 0 0 0 0
Other mental health disorders
Mental Health 0 0 0 0
Learning disabilities
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - idursulfase-IT
Other interventions - No IT treatment

Experimental: idursulfase-IT - 10 mg administered via IT using IDDD (intrathecal drug delivery device) once a month for 52 weeks.

Other: Nontreatment control - Patients will receive weekly standard of care treatment with IV Elaprase only.


Other interventions: idursulfase-IT
10mg

Other interventions: No IT treatment
Standard of Care

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from baseline in the GCA score after 12 months of treatment at visit week 52, as obtained by DAS-II testing
Timepoint [1] 0 0
Baseline to week 52
Secondary outcome [1] 0 0
Change from baseline in the adaptive behavior composite (ABC) score after 12 months of treatment at visit week 52, as obtained by VABS-II testing
Timepoint [1] 0 0
Baseline to week 52
Secondary outcome [2] 0 0
Change from baseline in the GCA score at visit weeks 16, 28 and 40 as obtained by DAS-II testing
Timepoint [2] 0 0
Baseline to week 40
Secondary outcome [3] 0 0
Change from baseline in the ABC score at visit weeks 16, 28 and 40 as obtained by VABS-II testing
Timepoint [3] 0 0
Baseline to week 40
Secondary outcome [4] 0 0
Change from baseline in standard scores at visit weeks 16, 28, 40 and 52 in cluster areas of the DAS-II
Timepoint [4] 0 0
Baseline to week 52
Secondary outcome [5] 0 0
Change from baseline in standard scores at visit weeks 16, 28, 40 and 52 of VABS-II domains
Timepoint [5] 0 0
Baseline to week 52
Secondary outcome [6] 0 0
Change from baseline in age equivalents at visit weeks 16, 28, 40 and 52 developmental quotients, and T-scores for the subtests of the DAS-II
Timepoint [6] 0 0
Baseline to week 52
Secondary outcome [7] 0 0
Change from baseline to visit weeks 16, 28, 40 and 52 in age equivalents, developmental quotients, and V-scale scores of the VABS-II subdomains
Timepoint [7] 0 0
Baseline to week 52
Secondary outcome [8] 0 0
Change from baseline to visit weeks 16, 28, 40 and 52 in the V-scale scores and observed maladaptive levels of the VABS-II Maladaptive Behavior Index and its subscales
Timepoint [8] 0 0
Baseline to week 52

Eligibility
Key inclusion criteria
Inclusion Criteria Inclusion Criteria for the Pivotal Study

Patients must meet all of the following criteria to be considered eligible for
randomization in the pivotal study:

1. The patient is male and is =3 and <18 years of age at the time of informed consent.

(Patients who are younger than 3 years of age may be enrolled in a separate substudy
provided that they meet other inclusion criteria, provided below.)

2. The patient must have a documented diagnosis of MPS II.

3. The patient has evidence at Screening of Hunter syndrome-related cognitive impairment
defined as follows:

A patient who is =3 and <13 years of age must have one of the following criteria (3a
OR 3b):

1. A GCA score =55 and =85 OR

2. If the patient has a GCA score at Screening >85, there must be evidence of a
decrease in GCA score of =10 points over 12 months from a previously documented
test result in observational study HGT-HIT-090.

A patient who is =13 and <18 years of age must have both of the following
criteria (3c AND 3d):

3. A GCA score of =55 and =85. AND

4. There must be evidence of a decrease in GCA score of =10 points over 12 months
from a previously documented

4. The patient has received and tolerated a minimum of 4 months of therapy with Elaprase
during the period immediately prior to Screening.

5. The patient must have sufficient auditory capacity, with a hearing aid(s), if needed,
in the Investigator's judgment to complete the required protocol testing and must be
compliant with wearing the hearing aid(s), if needed, on scheduled testing days.

6. The 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.
Consent of the patient's parent(s) or legally authorized guardian(s) and the patient's
assent, if applicable, must be obtained prior to the start of any study procedures.

Inclusion Criteria for the Substudy

Patients must meet all of the following criteria to be considered eligible for enrollment
in the separate substudy:

1. The patient is male and is <3 years of age at the time of informed consent.

2. The patient must have a documented diagnosis of MPS II.

3. The patient has evidence at Screening of Hunter syndrome-related cognitive impairment

4. The patient has received and tolerated a minimum of 4 months of therapy with Elaprase
during the period immediately prior to Screening.

5. The patient must have sufficient auditory capacity, with a hearing aid(s), if needed,
in the Investigator's judgment to complete the required protocol testing and must be
compliant with wearing the hearing aid(s), if needed, on scheduled testing days.

6. The 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.
Consent of the patient's parent(s) or legally authorized guardian(s) must be obtained
prior to the start of any study procedures.
Minimum age
No limit
Maximum age
18 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

Patients who meet any of the following criteria are not eligible to be randomized into the
pivotal study or enrolled in the separate substudy:

1. The patient has clinically significant non-Hunter syndrome-related CNS involvement
(such as Fragile-X syndrome) which is judged by the Investigator to be likely to
interfere with the accurate administration and interpretation of protocol assessments.

2. The patient has a large chromosomal deletion or complex rearrangement that includes a
deletion of the FMR1 and/or FMR2 genes.

3. The patient has a significant medical or psychiatric comorbidity(ies) that might
affect study data or confound the integrity of study results.

4. The patient has contra-indications for performance of lumbar puncture such as
musculoskeletal/spinal abnormalities or risk of abnormal bleeding.

5. 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.

6. The patient has an opening CSF pressure upon lumbar puncture that exceeds 30.0 cm H2O.

7. 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.

8. 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.

9. The patient has a history of poorly controlled seizure disorder.

10. 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.

11. The patient is enrolled in another clinical study that involves clinical investigation
or use of any investigational product (drug or [intrathecal/spinal] device) within 30
days prior to study enrollment or at any time during the study.

12. 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.

13. The patient has a condition that is contraindicated as described in the SOPH-A-PORT
Mini S IDDD Instructions for Use (IFU), including but not limited to the presence of a
CSF shunt device in the patient.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Current
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Women's and Children's Hospital, 72 King William Road - North Adelaide
Recruitment postcode(s) [1] 0 0
5006 - North Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
France
State/province [5] 0 0
Bron
Country [6] 0 0
Mexico
State/province [6] 0 0
Ciudad De México
Country [7] 0 0
Spain
State/province [7] 0 0
Madrid
Country [8] 0 0
United Kingdom
State/province [8] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Shire
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Study HGT-HIT-094 is a multicenter study designed to determine the effect on clinical
parameters of neurodevelopmental status of monthly IT administration of idursulfase-IT 10 mg
for 12 months in pediatric patients with Hunter syndrome and cognitive impairment who have
previously received and tolerated a minimum of 4 months of therapy with Elaprase.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Shire Study Physician
Address 0 0
Shire
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries
Contact person responsible for updating information