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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®

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ClinicalTrials.gov Identifier: NCT00920647
Recruitment Status : Completed
First Posted : June 15, 2009
Results First Posted : May 16, 2014
Last Update Posted : October 28, 2015
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hunter Syndrome
Interventions Other: Control
Drug: Idursulfase IT (1 mg)
Drug: Idursulfase IT (10 mg)
Drug: Idursulfase IT (30 mg)
Enrollment 16

Recruitment Details

The first patient enrolled on 18 November 2009.

Patients were assigned randomly to active dose or no treatment. A total of 16 patients were randomized, 4 to each dose group and the no treatment arm.

Pre-assignment Details  
Arm/Group Title Control Idursulfase IT (1 mg) Idursulfase IT (10 mg) Idursulfase IT (30 mg)
Hide Arm/Group Description Untreated Patients monthly using an intrathecal drug delivery device (IDDD) monthly using an intrathecal drug delivery device (IDDD) monthly using an intrathecal drug delivery device (IDDD)
Period Title: Overall Study
Started 4 4 4 4
Completed 4 4 4 4
Not Completed 0 0 0 0
Arm/Group Title Control Idursulfase IT (1 mg) Idursulfase IT (10 mg) Idursulfase IT (30 mg) Total
Hide Arm/Group Description Untreated Patients monthly using an intrathecal drug delivery device (IDDD) monthly using an intrathecal drug delivery device (IDDD) monthly using an intrathecal drug delivery device (IDDD) Total of all reporting groups
Overall Number of Baseline Participants 4 4 4 4 16
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 4 participants 4 participants 16 participants
<=18 years
4
 100.0%
4
 100.0%
4
 100.0%
4
 100.0%
16
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 4 participants 4 participants 4 participants 16 participants
8.64  (2.462) 5.61  (1.799) 4.34  (0.829) 6.91  (1.678) 6.38  (2.294)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 4 participants 4 participants 16 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
4
 100.0%
4
 100.0%
4
 100.0%
4
 100.0%
16
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 4 participants 4 participants 16 participants
United States 3 2 4 2 11
United Kingdom 1 2 0 2 5
1.Primary Outcome
Title Number of Serious Adverse Event (SAE)
Hide Description [Not Specified]
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Abnormalities Any Time Post-baseline ITT Population
Arm/Group Title Control Idursulfase IT (1 mg) Idursulfase IT (10 mg) Idursulfase IT (30 mg)
Hide Arm/Group Description:
Untreated Patients
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
Overall Number of Participants Analyzed 4 4 4 4
Measure Type: Number
Unit of Measure: events
0 8 3 3
2.Primary Outcome
Title Number of Treatment Emergent Adverse Event (AE)
Hide Description ITT patient population
Time Frame Baseline to week 23
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Idursulfase IT (1 mg) Idursulfase IT (10 mg) Idursulfase IT (30 mg)
Hide Arm/Group Description:
[Not Specified]
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
Overall Number of Participants Analyzed 4 4 4 4
Measure Type: Number
Unit of Measure: events
23 147 116 104
3.Primary Outcome
Title Safety Changes in Cerebrospinal Fluid (CSF)- White Blood Cells (WBC)
Hide Description White blood cell count in CSF was monitored throughout the study as a way of assessing any potential inflammation of the meninges induced by idursulfase-IT.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Abnormalities Any Time Post-baseline ITT Population
Arm/Group Title Control Idursulfase IT (1 mg) Idursulfase IT (10 mg) Idursulfase IT (30 mg)
Hide Arm/Group Description:
Untreated Patients
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
Overall Number of Participants Analyzed 4 4 4 4
Measure Type: Number
Unit of Measure: events
0 3 1 2
4.Primary Outcome
Title Safety: Development of Anti-idursulfase Antibodies (CSF)
Hide Description Reflects development of anti-idursulfase antibodies post baseline.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Abnormalities Any Time Post-baseline ITT Population
Arm/Group Title Control Idursulfase IT (1 mg) Idursulfase IT (10 mg) Idursulfase IT (30 mg)
Hide Arm/Group Description:
Untreated Patients
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
Overall Number of Participants Analyzed 4 4 4 4
Measure Type: Number
Unit of Measure: participants
0 0 0 0
5.Primary Outcome
Title Safety: Development of Anti-idursulfase Antibodies (Serum)
Hide Description [Not Specified]
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Development of antibodies post Baseline-ITT Population
Arm/Group Title Control Idursulfase IT (1 mg) Idursulfase IT (10 mg) Idursulfase IT (30 mg)
Hide Arm/Group Description:
Untreated Patients
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
Overall Number of Participants Analyzed 4 4 4 4
Measure Type: Number
Unit of Measure: participants
1 0 0 0
6.Primary Outcome
Title Clinically Significant ECG Findings at Any Time During the Study.
Hide Description Electrocardiogram (ECG) parameters included: heart rate, sinus rhythm, atrial/ventricular hypertrophy, PR, QRS, QT and QTc intervals.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Abnormalities Any Time Post-baseline ITT Population
Arm/Group Title Control Idursulfase IT (1 mg) Idursulfase IT (10 mg) Idursulfase IT (30 mg)
Hide Arm/Group Description:
Untreated Patients
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
Overall Number of Participants Analyzed 4 4 4 4
Measure Type: Number
Unit of Measure: participants
0 0 1 0
7.Secondary Outcome
Title Change From Baseline in CSF Glycosaminoglycans [GAGs] at Week 27
Hide Description Percent Change from Baseline to Week 27
Time Frame Baseline to Week 27
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Idursulfase IT (1 mg) Idursulfase IT (10 mg) Idursulfase IT (30 mg)
Hide Arm/Group Description:
Untreated Patients for 6 months, Observed Value
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
Overall Number of Participants Analyzed 4 4 4 4
Mean (Standard Error)
Unit of Measure: % change
6.68  (6.301) -79.03  (5.167) -90.30  (2.917) -88.87  (1.035)
8.Secondary Outcome
Title Level of Idursulfase in the CSF Compartment Resulting From Monthly Idursulfase IT Administrations
Hide Description Samples collected from patients treated at doses of 1 mg and 30 mg, as well as the control group, were below the lower limit of detection of the bioanalytical method (3.13 ng/mL)
Time Frame Week 27 (end of study)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Idursulfase IT (1mg) Idursulfase IT (10 mg) Idursulfase IT (30 mg)
Hide Arm/Group Description:
Untreated Patients
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
Overall Number of Participants Analyzed 4 4 4 4
Mean (Standard Deviation)
Unit of Measure: ng/mL
NA [1]   (NA) NA [2]   (NA) 6.74  (12.02) NA [3]   (NA)
[1]
Samples collected from patients treated in the control group were below the lower limit of detection of the bioanalytical method (3.13 ng/mL).
[2]
Samples collected from patients treated in the 1mg group were below the lower limit of detection of the bioanalytical method (3.13 ng/mL).
[3]
Samples collected from patients treated in the 30mg group were below the lower limit of detection of the bioanalytical method (3.13 ng/mL).
9.Secondary Outcome
Title Concentration of Idursulfase in Serum After Single Administration (Week 3) in Conjunction With Elaprase
Hide Description Values below lower limit of quantitation (LLOQ) are listed as 0.
Time Frame Weeks 3
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

Data were not available for the calculations in the patients of 1 mg idursulfase-IT group at Week 3.

Serum samples were not obtained from one patient in the 30mg Idursulfase-IT group at Week 3 after IV and IT administration.

Arm/Group Title Idursulfase IT (1 mg) Idursulfase IT (10 mg) Idursulfase IT (30 mg)
Hide Arm/Group Description:
monthly using an intrathecal drug delivery device (IDDD.
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
Overall Number of Participants Analyzed 0 4 3
Mean (Standard Deviation)
Unit of Measure: min*ng/mL
140022  (45479) 228840  (37909)
10.Secondary Outcome
Title Concentration of Idursulfase in Serum After Repeated Doses of Intrathecal Idursulfase-IT Given in Conjunction With Elaprase
Hide Description [Not Specified]
Time Frame Weeks 23
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Only 1 patient out of 4 in the 1mg dose yielded sufficient data to calculate AUC.
Arm/Group Title Idursulfase IT (1 mg) Idursulfase IT (10 mg) Idursulfase IT (30 mg)
Hide Arm/Group Description:

monthly using an intrathecal drug delivery device (IDDD)

Value represents concentration at 36 hours post drug administration.

monthly using an intrathecal drug delivery device (IDDD)

Value represents concentration at 24 hours post drug administration

monthly using an intrathecal drug delivery device (IDDD)

Value represents concentration at 36 hours post drug administration

Overall Number of Participants Analyzed 1 4 4
Mean (Standard Deviation)
Unit of Measure: min*ng/mL
31481 150544  (43871) 174247  (49795)
11.Secondary Outcome
Title % Change From Baseline in Urinary GAG
Hide Description [Not Specified]
Time Frame Baseline to Week 27
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Control Idursulfase IT (1 mg) Idursulfase IT (10 mg) Idursulfase IT (30 mg)
Hide Arm/Group Description:
Untreated Patients, Observed Value
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
monthly using an intrathecal drug delivery device (IDDD)
Overall Number of Participants Analyzed 4 4 4 4
Mean (Standard Error)
Unit of Measure: % Change
-7.67  (20.820) 37.83  (27.971) -22.38  (4.840) 29.70  (13.700)
Time Frame Time of informed consent until 30 days after the patients end of study visit.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Control Idursulfase IT (1 mg) Idursulfase IT (10 mg) Idursulfase IT (30 mg)
Hide Arm/Group Description Untreated Patients monthly using an intrathecal drug delivery device (IDDD) monthly using an intrathecal drug delivery device (IDDD) monthly using an intrathecal drug delivery device (IDDD)
All-Cause Mortality
Control Idursulfase IT (1 mg) Idursulfase IT (10 mg) Idursulfase IT (30 mg)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Control Idursulfase IT (1 mg) Idursulfase IT (10 mg) Idursulfase IT (30 mg)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/4 (0.00%)      3/4 (75.00%)      2/4 (50.00%)      2/4 (50.00%)    
Gastrointestinal disorders         
Vomiting  1 [1]  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Infections and infestations         
Implant site infection  1 [2]  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 2/4 (50.00%)  3
Injury, poisoning and procedural complications         
Device dislocation  1  0/4 (0.00%)  0 1/4 (25.00%)  1 1/4 (25.00%)  1 0/4 (0.00%)  0
Complication of device insertion  1 [3]  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Device breakage  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Device connection issue  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Device failure  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Device malfunction  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Wound dehiscence  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Metabolism and nutrition disorders         
Dehydration  1 [1]  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.0)
[1]
Event not related to investigational treatment or device
[2]
Event considered possibly related to the device
[3]
Untreated control patients did not have IDDD implanted
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Control Idursulfase IT (1 mg) Idursulfase IT (10 mg) Idursulfase IT (30 mg)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/4 (100.00%)      4/4 (100.00%)      4/4 (100.00%)      4/4 (100.00%)    
Blood and lymphatic system disorders         
Anaemia  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 1/4 (25.00%)  1
Eosinophilia  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Lymphadenopathy  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Microcystosis  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Cardiac disorders         
Atrioventricular Block First Degree  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Cyanosis  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Left Atrial Hypertrophy  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Left Ventricular Hypertrophy  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Mitral Valve Incompetence  1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0
Mitral Valve Prolapse  1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0
Tachycardia  1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0
Congenital, familial and genetic disorders         
Bicuspid Aortic Valve  1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0
Ear and labyrinth disorders         
Otorrhoea  1  0/4 (0.00%)  0 1/4 (25.00%)  2 2/4 (50.00%)  2 2/4 (50.00%)  2
Ear Pain  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Middle Ear Infusion  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Motion Sickness  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Tympanic Membrane Disorder  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Eye disorders         
Ocular Hyperaemia  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Gastrointestinal disorders         
Vomiting  1  1/4 (25.00%)  1 2/4 (50.00%)  7 3/4 (75.00%)  7 1/4 (25.00%)  1
Diarrhoea  1  0/4 (0.00%)  0 2/4 (50.00%)  4 1/4 (25.00%)  2 0/4 (0.00%)  0
Abdominal Distension  1  1/4 (25.00%)  1 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Nausea  1  0/4 (0.00%)  0 2/4 (50.00%)  2 0/4 (0.00%)  0 0/4 (0.00%)  0
Constipation  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Dysphagia  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Gastrooesophageal Reflux Disease  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Umbilical Hernia  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
General disorders         
Pyrexia  1  0/4 (0.00%)  0 2/4 (50.00%)  4 0/4 (0.00%)  0 2/4 (50.00%)  3
Catheter Related Complication  1  0/4 (0.00%)  0 1/4 (25.00%)  1 1/4 (25.00%)  1 1/4 (25.00%)  2
Fatigue  1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Implant Site Swelling  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  2 1/4 (25.00%)  1
Catheter Site Erythema  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Catheter Site Haematoma  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Extravasation  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Implant Site Effusion  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Implant Site Erythema  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Implant Site Scar  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Infusion Site Extravasation  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  2
Odema Peripheral  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Immune system disorders         
Seasonal Allergy  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Infections and infestations         
Upper respiratory tract  1  1/4 (25.00%)  1 3/4 (75.00%)  3 3/4 (75.00%)  3 4/4 (100.00%)  5
Implant site infection  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 2/4 (50.00%)  4
Otitis Media  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 2/4 (50.00%)  2
Anorectal Infection  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Ear Infection  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Eye Infection  1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0
Gastrointestinal Infection  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Herpes Zoster  1  0/4 (0.00%)  0 1/4 (25.00%)  2 0/4 (0.00%)  0 0/4 (0.00%)  0
Rhinitis  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Urinary Tract Infection  1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0
Traumatic Lumbar Puncture  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Injury, poisoning and procedural complications         
Procedural Pain  1  3/4 (75.00%)  3 4/4 (100.00%)  5 4/4 (100.00%)  7 2/4 (50.00%)  2
Arthropod Bite  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 1/4 (25.00%)  1
Contusion  1  0/4 (0.00%)  0 0/4 (0.00%)  0 2/4 (50.00%)  2 0/4 (0.00%)  0
Device Dislocation  1  0/4 (0.00%)  0 1/4 (25.00%)  1 1/4 (25.00%)  1 0/4 (0.00%)  0
Excoriation  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  2 1/4 (25.00%)  1
Procedural Site Reaction  1  0/4 (0.00%)  0 0/4 (0.00%)  0 2/4 (50.00%)  2 0/4 (0.00%)  0
Agitation Post-Operative  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Burns First Degree  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Complication of Device Insertion  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Device Breakage  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Device Connection Issue  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Device Failure  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Device Malfunction  1  0/4 (0.00%)  0 1/4 (25.00%)  3 0/4 (0.00%)  0 0/4 (0.00%)  0
Drug Delivery System Malfunction  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Medical Device Complication  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Procedural Complication  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Scratch  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Skin Laceration  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Suture Related Complication  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Thermal Burn  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Wound Dehiscence  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Investigations         
Blood Pressure Diastolic Decreased  1  0/4 (0.00%)  0 2/4 (50.00%)  6 3/4 (75.00%)  9 2/4 (50.00%)  10
Blood Pressure Systolic Increased  1  1/4 (25.00%)  1 2/4 (50.00%)  10 2/4 (50.00%)  5 2/4 (50.00%)  8
Blood Pressure Systolic Decreased  1  0/4 (0.00%)  0 1/4 (25.00%)  7 2/4 (50.00%)  3 2/4 (50.00%)  6
Heart Rate Decreased  1  1/4 (25.00%)  1 2/4 (50.00%)  8 1/4 (25.00%)  2 1/4 (25.00%)  1
Blood Pressure Decreased  1  0/4 (0.00%)  0 2/4 (50.00%)  4 2/4 (50.00%)  5 0/4 (0.00%)  0
Blood Pressure Diastolic Increased  1  1/4 (25.00%)  1 1/4 (25.00%)  1 1/4 (25.00%)  2 1/4 (25.00%)  5
Protein Total Decreased  1  0/4 (0.00%)  0 1/4 (25.00%)  1 2/4 (50.00%)  5 1/4 (25.00%)  1
Body Temperature Decreased  1  0/4 (0.00%)  0 1/4 (25.00%)  3 1/4 (25.00%)  1 1/4 (25.00%)  1
CSF Cell Count Increased  1  0/4 (0.00%)  0 1/4 (25.00%)  2 1/4 (25.00%)  1 1/4 (25.00%)  2
CSF Protein Increased  1  0/4 (0.00%)  0 1/4 (25.00%)  2 1/4 (25.00%)  1 1/4 (25.00%)  2
Cardiac Murmur  1  0/4 (0.00%)  0 2/4 (50.00%)  2 0/4 (0.00%)  0 1/4 (25.00%)  2
Blood Chloride Increased  1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Blood Pressure Increased  1  1/4 (25.00%)  1 0/4 (0.00%)  0 1/4 (25.00%)  2 0/4 (0.00%)  0
Blood Thyroid Stimulating Hormone Decreased  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 1/4 (25.00%)  1
Body Temperature Increased  1  0/4 (0.00%)  0 1/4 (25.00%)  1 1/4 (25.00%)  1 0/4 (0.00%)  0
CSF Glucose Decreased  1  0/4 (0.00%)  0 0/4 (0.00%)  0 2/4 (50.00%)  2 0/4 (0.00%)  0
Red Blood Cells CSF Positive  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 1/4 (25.00%)  1
Activated Partial Thromboplastin Time Prolonged  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Alanine Aminotransferase Increased  1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0
Blood Calcium Decreased  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Blood Phosphorus Decreased  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Blood Thyroid Stimulating Hormone Increased  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Blood Triglycerides Increased  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
CSF White Blood Cell Count Increased  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Electrocardiogram QT Prolonged  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Haematocrit Decreased  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Haemoglobin Decreased  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Heart Sounds Abnormal  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Neutrophil count decreased  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Mean cell volume abnormal  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  2 0/4 (0.00%)  0
Oxygen Saturation Decreased  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
PCO2 Decreased  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Red Blood Cell Count Decreased  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Respiratory Rate Decreased  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Respiratory Rate Increased  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Thyroxine Decreased  1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0
Vitamin D Decreased  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Metabolism and nutrition disorders         
Decreased Appetite  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Dehydration  1  0/4 (0.00%)  0 1/4 (25.00%)  2 0/4 (0.00%)  0 0/4 (0.00%)  0
Pica  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Back Pain  1  0/4 (0.00%)  0 1/4 (25.00%)  1 1/4 (25.00%)  1 0/4 (0.00%)  0
Neck Pain  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Pain in Extremity  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Scoliosis  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Tendon Disorder  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Toe Walking  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Nervous system disorders         
Headache  1  1/4 (25.00%)  1 0/4 (0.00%)  0 3/4 (75.00%)  3 0/4 (0.00%)  0
Clonus  1  0/4 (0.00%)  0 1/4 (25.00%)  2 0/4 (0.00%)  0 2/4 (50.00%)  5
Hyperreflexia  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 1/4 (25.00%)  1
Psychomotor Hyperactivity  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  2 1/4 (25.00%)  1
Pyramidal Tract Syndrome  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 1/4 (25.00%)  1
Carpal Tunnel Syndrome  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Dyskinesia  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Sensory Integrative Dysfunction  1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0
Syncope  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Psychiatric disorders         
Abnormal Behaviour  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Aggression  1  0/4 (0.00%)  0 1/4 (25.00%)  3 0/4 (0.00%)  0 0/4 (0.00%)  0
Agitation  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Anxiety  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Insomnia  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Personality Change  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Staring  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Renal and urinary disorders         
Urinary Incontinence  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Nasal Congestion  1  0/4 (0.00%)  0 1/4 (25.00%)  3 0/4 (0.00%)  0 1/4 (25.00%)  1
Aspiration  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Choking  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Cough  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  3
Epistaxis  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Hypoxia  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Oropharyngeal Pain  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Productive Cough  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Rhinorrhoea  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Sneezing  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Stridor  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Upper Respiratory Tract Congestion  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Skin and subcutaneous tissue disorders         
Erythema  1  0/4 (0.00%)  0 1/4 (25.00%)  1 1/4 (25.00%)  1 1/4 (25.00%)  1
Rash  1  0/4 (0.00%)  0 0/4 (0.00%)  0 2/4 (50.00%)  2 0/4 (0.00%)  0
Dermatitis Diaper  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Dry Skin  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Eczema  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Pruritus  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Swelling Face  1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0
Urticaria  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Surgical and medical procedures         
Tooth Extractions  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0 0/4 (0.00%)  0
Vascular disorders         
Blood Pressure Fluctuation  1  0/4 (0.00%)  0 0/4 (0.00%)  0 2/4 (50.00%)  3 0/4 (0.00%)  0
Flushing  1  0/4 (0.00%)  0 0/4 (0.00%)  0 2/4 (50.00%)  4 0/4 (0.00%)  0
Haematoma  1  0/4 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1
Hypotension  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/4 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.0)

Untreated control group were not implanted with IDDD.

Concentration of idursulfase in all CSF samples post single dose of idursulfase-IT were below LLOQ(Lower limit of quantitation) of the bioanalytical method therefore no results are reported.

Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Shire’s agreements with investigators vary. All agreements provide Shire the right to embargo communications regarding trial results prior to public release for a period ≤180 days from the time submitted to Shire for review. Shire does not prohibit publication, but can require the removal of confidential information(excluding trial results) and can request postponement of a single-center publication until after disclosure of the trial’s multi-center publication.
Results Point of Contact
Name/Title: MedINfo
Organization: Shire Human Genetic Therapies Medical Information
Phone: 1-866-888-0660 ext 2
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00920647     History of Changes
Other Study ID Numbers: HGT-HIT-045
2010-020048-36 ( EudraCT Number )
First Submitted: June 12, 2009
First Posted: June 15, 2009
Results First Submitted: October 31, 2013
Results First Posted: May 16, 2014
Last Update Posted: October 28, 2015