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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02055118




Registration number
NCT02055118
Ethics application status
Date submitted
17/01/2014
Date registered
4/02/2014

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - 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.


Treatment: Other: idursulfase-IT
10mg

Other interventions: No IT treatment
Standard of Care

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in the Differential Ability Scales, Second Edition (DAS-II) General Conceptual Ability (GCA) Standard Score at Week 52
Timepoint [1] 0 0
Baseline, Week 52
Secondary outcome [1] 0 0
Change From Baseline in the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Adaptive Behavior Composite (ABC) Score at Week 52
Timepoint [1] 0 0
Baseline, Week 52
Secondary outcome [2] 0 0
Change From Baseline in the Differential Ability Scales, Second Edition (DAS-II) General Conceptual Ability (GCA) Standard Score at Weeks 16, 28 and 40
Timepoint [2] 0 0
Baseline, Week 16, Week 28 and Week 40
Secondary outcome [3] 0 0
Change From Baseline in the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Adaptive Behavior Composite (ABC) Score at Week 16, 28 and 40
Timepoint [3] 0 0
Baseline, Week 16, Week 28 and Week 40
Secondary outcome [4] 0 0
Change From Baseline in Differential Ability Scales, Second Edition (DAS-II) Cluster Standard Scores at Weeks 16, 28, 40 and 52
Timepoint [4] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [5] 0 0
Change From Baseline in Vineland Adaptive Behavior Scales, Second Edition (VABS-II) Standard Scores of Other Domains at Weeks 16, 28, 40, 52
Timepoint [5] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [6] 0 0
Change From Baseline of Age Equivalent Score for Early Years of Core Subtests of the Differential Ability Scales, Second Edition (DAS-II) at Weeks 16, 28, 40 and 52
Timepoint [6] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [7] 0 0
Change From Baseline of Age Equivalents for School Age of Core Subtests of the Differential Ability Scales, Second Edition (DAS-II) at Weeks 16, 28, 40 and 52
Timepoint [7] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [8] 0 0
Change From Baseline of Development Quotients for Early Years of Core Subtests of the Differential Ability Scales, Second Edition (DAS-II) at Weeks 16, 28, 40 and 52
Timepoint [8] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [9] 0 0
Change From Baseline of Development Quotients for School Age of Core Subtests of the Differential Ability Scales, Second Edition (DAS-II) at Weeks 16, 28, 40 and 52
Timepoint [9] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [10] 0 0
Change From Baseline of T-scores for Early Years of Core Subtests of the Differential Ability Scale, Second Edition (DAS-II) at Weeks 16, 28, 40 and 52
Timepoint [10] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [11] 0 0
Change From Baseline of T-scores for School Age of Core Subtests of the Differential Ability Scale, Second Edition (DAS-II) at Weeks 16, 28, 40 and 52
Timepoint [11] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [12] 0 0
Change From Baseline of Age Equivalents Scores of Sub-domains of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Weeks 16, 28, 40 and 52
Timepoint [12] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [13] 0 0
Change From Baseline of Development Quotients of Sub-domains of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Weeks 16, 28, 40 and 52
Timepoint [13] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [14] 0 0
Change From Baseline of V-Scale Scores of Sub-domains of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Weeks 16, 28, 40 and 52
Timepoint [14] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [15] 0 0
Change From Baseline of V-Scale Scores of Maladaptive Behavior Index and Its Sub-scales at Weeks 16, 28, 40 and 52
Timepoint [15] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [16] 0 0
Observed Maladaptive Levels of Maladaptive Behavior Index and Its Sub-scales of Vineland Adaptive Behavior Scales, Second Edition (VABS-II)
Timepoint [16] 0 0
Baseline, Week 16, Week 28, Week 40 and Week 52
Secondary outcome [17] 0 0
Maximum Observed Drug Concentration (Cmax) of Idursulfase After IT Administration
Timepoint [17] 0 0
Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48
Secondary outcome [18] 0 0
Time to Reach Maximum Drug Concentration (Tmax) of Idursulfase After IT Administration
Timepoint [18] 0 0
Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48
Secondary outcome [19] 0 0
Area Under the Concentration Versus Time Curve From Zero From the Time of Dosing to the Last Measurable Concentration (AUC0-t) of Idursulfase After IT Administration
Timepoint [19] 0 0
Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48
Secondary outcome [20] 0 0
Terminal Half-life (t1/2) of Idursulfase After IT Administration
Timepoint [20] 0 0
Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48
Secondary outcome [21] 0 0
Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed (CL/F) of Idursulfase After IT Administration
Timepoint [21] 0 0
Pre-dose, 30, 60, 120 minutes, 4, 6, 8, 12, 24, 30 and 36 hour (h) post-dose on Weeks 4, 24, and 48
Secondary outcome [22] 0 0
Change From Baseline in the Concentration of Glycosaminoglycans (GAG) in Cerebrospinal Fluid (CSF) at Week 52
Timepoint [22] 0 0
Baseline, Week 52
Secondary outcome [23] 0 0
Concentration of Idursulfase in Cerebrospinal Fluid (CSF)
Timepoint [23] 0 0
Pre-dose on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [24] 0 0
Participant Response to Quality of Life EuroQol-5D (EQ-5D) Questionnaire at Week 52
Timepoint [24] 0 0
Week 52
Secondary outcome [25] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Intrathecal Drug Delivery Device (IDDD)-Related Adverse Events
Timepoint [25] 0 0
From start of study treatment up to Week 53
Secondary outcome [26] 0 0
Composite Scores of Bayley Scales of Infant Development (BSID-III) Scale in Substudy Population
Timepoint [26] 0 0
Baseline up to Week 52
Secondary outcome [27] 0 0
Percentile Scores of Bayley Scales of Infant Development (BSID-III) Scale in Substudy Population
Timepoint [27] 0 0
Baseline up to Week 52
Secondary outcome [28] 0 0
Age Equivalent Scores of Bayley Scales of Infant Development (BSID-III) Scale in Substudy Population
Timepoint [28] 0 0
Baseline up to Week 52
Secondary outcome [29] 0 0
Chronological Age of Bayley Scales of Infant Development (BSID-III) Scale in Substudy Population
Timepoint [29] 0 0
Baseline up to Week 52
Secondary outcome [30] 0 0
Development Quotient (DQ) of Bayley Scales of Infant Development (BSID-III) Scale in Substudy Population
Timepoint [30] 0 0
Baseline up to Week 52
Secondary outcome [31] 0 0
Raw Scores of Bayley Scales of Infant Development (BSID-III) Scale in Substudy Population
Timepoint [31] 0 0
Baseline up 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
Sex
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
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Completed
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
Accrual to date
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
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Takeda
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Available to whom?
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/takeda/


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.