Trial Outcomes & Findings for 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® (NCT NCT00920647)

NCT ID: NCT00920647

Last Updated: 2021-06-28

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

16 participants

Primary outcome timeframe

6 months

Results posted on

2021-06-28

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Control Untreated Patients	Idursulfase IT (1 mg) monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (10 mg) monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (30 mg) monthly using an intrathecal drug delivery device (IDDD)
Overall Study STARTED	4	4	4	4
Overall Study COMPLETED	4	4	4	4
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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®

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Control n=4 Participants Untreated Patients	Idursulfase IT (1 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (10 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (30 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Total n=16 Participants Total of all reporting groups
Age, Categorical <=18 years	4 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	16 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Continuous	8.64 years STANDARD_DEVIATION 2.462 • n=5 Participants	5.61 years STANDARD_DEVIATION 1.799 • n=7 Participants	4.34 years STANDARD_DEVIATION 0.829 • n=5 Participants	6.91 years STANDARD_DEVIATION 1.678 • n=4 Participants	6.38 years STANDARD_DEVIATION 2.294 • n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	16 Participants n=21 Participants
Region of Enrollment United States	3 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	11 Participants n=21 Participants
Region of Enrollment United Kingdom	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Abnormalities Any Time Post-baseline ITT Population

Outcome measures

Outcome measures
Measure	Control n=4 Participants Untreated Patients	Idursulfase IT (1 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (10 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (30 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)
Number of Serious Adverse Event (SAE)	0 events	8 events	3 events	3 events

PRIMARY outcome

Timeframe: Baseline to week 23

ITT patient population

Outcome measures

Outcome measures
Measure	Control n=4 Participants Untreated Patients	Idursulfase IT (1 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (10 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (30 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)
Number of Treatment Emergent Adverse Event (AE)	23 events	147 events	116 events	104 events

PRIMARY outcome

Timeframe: 6 months

Population: Abnormalities Any Time Post-baseline ITT Population

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.

Outcome measures

Outcome measures
Measure	Control n=4 Participants Untreated Patients	Idursulfase IT (1 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (10 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (30 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)
Safety Changes in Cerebrospinal Fluid (CSF)- White Blood Cells (WBC)	0 events	3 events	1 events	2 events

PRIMARY outcome

Timeframe: 6 months

Population: Abnormalities Any Time Post-baseline ITT Population

Reflects development of anti-idursulfase antibodies post baseline.

Outcome measures

Outcome measures
Measure	Control n=4 Participants Untreated Patients	Idursulfase IT (1 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (10 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (30 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)
Safety: Development of Anti-idursulfase Antibodies (CSF)	0 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: 6 months

Population: Development of antibodies post Baseline-ITT Population

Outcome measures

Outcome measures
Measure	Control n=4 Participants Untreated Patients	Idursulfase IT (1 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (10 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (30 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)
Safety: Development of Anti-idursulfase Antibodies (Serum)	1 participants	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: 6 months

Population: Abnormalities Any Time Post-baseline ITT Population

Electrocardiogram (ECG) parameters included: heart rate, sinus rhythm, atrial/ventricular hypertrophy, PR, QRS, QT and QTc intervals.

Outcome measures

Outcome measures
Measure	Control n=4 Participants Untreated Patients	Idursulfase IT (1 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (10 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (30 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)
Clinically Significant ECG Findings at Any Time During the Study.	0 participants	0 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Baseline to Week 27

Percent Change from Baseline to Week 27

Outcome measures

Outcome measures
Measure	Control n=4 Participants Untreated Patients	Idursulfase IT (1 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (10 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (30 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)
Change From Baseline in CSF Glycosaminoglycans [GAGs] at Week 27	6.68 % change Standard Error 6.301	-79.03 % change Standard Error 5.167	-90.30 % change Standard Error 2.917	-88.87 % change Standard Error 1.035

SECONDARY outcome

Timeframe: Week 27 (end of study)

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)

Outcome measures

Outcome measures
Measure	Control n=4 Participants Untreated Patients	Idursulfase IT (1 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (10 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (30 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)
Level of Idursulfase in the CSF Compartment Resulting From Monthly Idursulfase IT Administrations	NA ng/mL Standard Deviation NA Samples collected from patients treated in the control group were below the lower limit of detection of the bioanalytical method (3.13 ng/mL).	NA ng/mL Standard Deviation NA Samples collected from patients treated in the 1mg group were below the lower limit of detection of the bioanalytical method (3.13 ng/mL).	6.74 ng/mL Standard Deviation 12.02	NA ng/mL Standard Deviation NA Samples collected from patients treated in the 30mg group were below the lower limit of detection of the bioanalytical method (3.13 ng/mL).

SECONDARY outcome

Timeframe: Weeks 3

Population: 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.

Values below lower limit of quantitation (LLOQ) are listed as 0.

Outcome measures

Outcome measures
Measure	Control Untreated Patients	Idursulfase IT (1 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (10 mg) n=3 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (30 mg) monthly using an intrathecal drug delivery device (IDDD)
Concentration of Idursulfase in Serum After Single Administration (Week 3) in Conjunction With Elaprase	—	140022 min*ng/mL Standard Deviation 45479	228840 min*ng/mL Standard Deviation 37909	—

SECONDARY outcome

Timeframe: Weeks 23

Population: Only 1 patient out of 4 in the 1mg dose yielded sufficient data to calculate AUC.

Outcome measures

Outcome measures
Measure	Control n=1 Participants Untreated Patients	Idursulfase IT (1 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (10 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (30 mg) monthly using an intrathecal drug delivery device (IDDD)
Concentration of Idursulfase in Serum After Repeated Doses of Intrathecal Idursulfase-IT Given in Conjunction With Elaprase	31481 min*ng/mL	150544 min*ng/mL Standard Deviation 43871	174247 min*ng/mL Standard Deviation 49795	—

SECONDARY outcome

Timeframe: Baseline to Week 27

Outcome measures

Outcome measures
Measure	Control n=4 Participants Untreated Patients	Idursulfase IT (1 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (10 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (30 mg) n=4 Participants monthly using an intrathecal drug delivery device (IDDD)
% Change From Baseline in Urinary GAG	-7.67 % Change Standard Error 20.820	37.83 % Change Standard Error 27.971	-22.38 % Change Standard Error 4.840	29.70 % Change Standard Error 13.700

Adverse Events

Control

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Idursulfase IT (1 mg)

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

Idursulfase IT (10 mg)

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Idursulfase IT (30 mg)

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Control n=4 participants at risk Untreated Patients	Idursulfase IT (1 mg) n=4 participants at risk monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (10 mg) n=4 participants at risk monthly using an intrathecal drug delivery device (IDDD)	Idursulfase IT (30 mg) n=4 participants at risk monthly using an intrathecal drug delivery device (IDDD)
Infections and infestations Implant site infection	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	25.0% 1/4 • Number of events 1 • Time of informed consent until 30 days after the patients end of study visit.	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	50.0% 2/4 • Number of events 3 • Time of informed consent until 30 days after the patients end of study visit.
Metabolism and nutrition disorders Dehydration	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	25.0% 1/4 • Number of events 1 • Time of informed consent until 30 days after the patients end of study visit.	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.
Gastrointestinal disorders Vomiting	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	25.0% 1/4 • Number of events 1 • Time of informed consent until 30 days after the patients end of study visit.	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.
Injury, poisoning and procedural complications Device dislocation	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	25.0% 1/4 • Number of events 1 • Time of informed consent until 30 days after the patients end of study visit.	25.0% 1/4 • Number of events 1 • Time of informed consent until 30 days after the patients end of study visit.	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.
Injury, poisoning and procedural complications Complication of device insertion	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	25.0% 1/4 • Number of events 1 • Time of informed consent until 30 days after the patients end of study visit.	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.
Injury, poisoning and procedural complications Device breakage	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	25.0% 1/4 • Number of events 1 • Time of informed consent until 30 days after the patients end of study visit.	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.
Injury, poisoning and procedural complications Device connection issue	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	25.0% 1/4 • Number of events 1 • Time of informed consent until 30 days after the patients end of study visit.	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.
Injury, poisoning and procedural complications Device failure	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	25.0% 1/4 • Number of events 1 • Time of informed consent until 30 days after the patients end of study visit.	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.
Injury, poisoning and procedural complications Device malfunction	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	25.0% 1/4 • Number of events 1 • Time of informed consent until 30 days after the patients end of study visit.	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	25.0% 1/4 • Number of events 1 • Time of informed consent until 30 days after the patients end of study visit.	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.	0.00% 0/4 • Time of informed consent until 30 days after the patients end of study visit.

Other adverse events

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER