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Safety and Clinical Outcomes in Hunter Syndrome Patients 5 Years of Age and Younger Receiving Idursulfase Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00607386
Recruitment Status : Completed
First Posted : February 5, 2008
Results First Posted : November 7, 2013
Last Update Posted : October 28, 2015
Sponsor:
Collaborators:
Covance
PharmaNet
PRA Health Sciences
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Hunter Syndrome
Mucopolysaccharidosis II
MPS II
Intervention Biological: Idursulfase
Enrollment 28
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Idursulfase
Hide Arm/Group Description Open-label treatment with idursulfase
Period Title: Overall Study
Started 28
Completed 27
Not Completed 1
Reason Not Completed
Physician Decision             1
Arm/Group Title Idursulfase
Hide Arm/Group Description Open-label treatment with idursulfase
Overall Number of Baseline Participants 28
Hide Baseline Analysis Population Description
Safety population was defined as all enrolled participants who received at least one study dose (or any portion of a dose) of idursulfase.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 28 participants
4.0  (1.62)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants
Female
0
   0.0%
Male
28
 100.0%
Baseline Normalized Urinary Glycosaminoglycan (GAG) Level  
Mean (Standard Deviation)
Unit of measure:  Microgram per milligram creatinine
Number Analyzed 28 participants
738.3  (165.21)
1.Primary Outcome
Title Safety Evaluation
Hide Description An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered as a pharmaceutical product that did not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Number of participants with AEs occurred after start of study treatment until 30 days after the last infusion of idursulfase, were reported.
Time Frame From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all enrolled participants who received at least one study dose (or any portion of a dose) of idursulfase.
Arm/Group Title Idursulfase
Hide Arm/Group Description:
Open-label treatment with idursulfase
Overall Number of Participants Analyzed 28
Measure Type: Number
Unit of Measure: participants
Experienced at least one adverse event (AE) 28
Deaths 0
Discontinued due to an AE 0
Experienced at least one drug-related AE 16
Experienced at least one serious AE (SAE) 13
Experienced at least one severe AE 2
Experienced at least one infusion-related AE 16
2.Secondary Outcome
Title Mean Change From Baseline to Week 53 in Normalized Urinary Glycosaminoglycan (GAG) Levels
Hide Description Analysis of urinary GAG levels was performed at baseline, Week 18, Week 36, and Week 53 as an assessment of the pharmacodynamic effects of Elaprase (idursulfase).
Time Frame Baseline, Weeks 18, 36 and 53
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. In the categories listed below, 'N' signifies the number of participants evaluable for the timepoint.
Arm/Group Title Idursulfase
Hide Arm/Group Description:
Open-label treatment with idursulfase
Overall Number of Participants Analyzed 28
Mean (Standard Deviation)
Unit of Measure: microgram/milligram creatinine
Baseline (N=28) 738.3  (165.21)
Change at Week 18 (N=27) -368.0  (165.44)
Change at Week 36 (N=27) -400.3  (180.27)
Change at Week 53 (N=27) -402.4  (162.13)
3.Secondary Outcome
Title Single- and Repeat-Dose Pharmacokinetics - Maximum Observed Serum Concentration (Cmax)
Hide Description [Not Specified]
Time Frame Weeks 1 and 27
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population was defined as all enrolled participants who had at least one serum concentration measurement available. In the categories listed below, “N” signifies the number of participants evaluable for the timepoint.
Arm/Group Title Idursulfase
Hide Arm/Group Description:
Open-label treatment with idursulfase
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter
Week 1 (N=27) 1333  (817)
Week 27 (N=19) 1032  (590)
4.Secondary Outcome
Title Single- and Repeat-Dose Pharmacokinetics - Time of Maximum Observed Serum Concentration (Tmax)
Hide Description [Not Specified]
Time Frame Weeks 1 and 27
Hide Outcome Measure Data
Hide Analysis Population Description
PK population. In the categories listed below, “N” signifies the number of participants evaluable for the timepoint.
Arm/Group Title Idursulfase
Hide Arm/Group Description:
Open-label treatment with idursulfase
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: minutes
Week 1 (N=27) 163  (28)
Week 27 (N=19) 167  (32)
5.Secondary Outcome
Title Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to the Final Time Point With a Concentration of at Least Lower Limit of Quantitation (AUClast)
Hide Description [Not Specified]
Time Frame Weeks 1 and 27
Hide Outcome Measure Data
Hide Analysis Population Description
PK population. In the categories listed below, “N” signifies the number of participants evaluable for the timepoint.
Arm/Group Title Idursulfase
Hide Arm/Group Description:
Open-label treatment with idursulfase
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: minute*nanogram per milliliter
Week 1 (N=27) 196526  (71779)
Week 27 (N=19) 174869  (109118)
6.Secondary Outcome
Title Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf)
Hide Description [Not Specified]
Time Frame Weeks 1 and 27
Hide Outcome Measure Data
Hide Analysis Population Description
PK population with evaluable participants for this endpoint. In the categories listed below, "N" signifies the number of participants evaluable for the timepoint.
Arm/Group Title Idursulfase
Hide Arm/Group Description:
Open-label treatment with idursulfase
Overall Number of Participants Analyzed 26
Mean (Standard Deviation)
Unit of Measure: minute*nanogram per milliliter
Week 1 (N=26) 224343  (76944)
Week 27 (N=18) 201130  (117575)
7.Secondary Outcome
Title Single- and Repeat-Dose Pharmacokinetics - Elimination Half-Life (t1/2)
Hide Description t1/2 refers to the elimination of the drug. It is the time taken for the blood plasma concentration to reach half the concentration in the terminal phase of elimination. It is expressed in minutes and derived from the terminal slope of the concentration versus time curve.
Time Frame Weeks 1 and 27
Hide Outcome Measure Data
Hide Analysis Population Description
PK population with evaluable participants for this endpoint. In the categories listed below, "N" signifies the number of participants evaluable for the timepoint.
Arm/Group Title Idursulfase
Hide Arm/Group Description:
Open-label treatment with idursulfase
Overall Number of Participants Analyzed 26
Mean (Standard Deviation)
Unit of Measure: minutes
Week 1 (N=26) 160  (69)
Week 27 (N=18) 109  (43)
8.Secondary Outcome
Title Single- and Repeat-Dose Pharmacokinetics - Mean Residence Time From Time 0 to Infinity (MRTinf)
Hide Description MRTinf is an average duration of the drug in the body from time zero to infinity, and is expressed in minutes.
Time Frame Weeks 1 and 27
Hide Outcome Measure Data
Hide Analysis Population Description
PK population with evaluable participants for this endpoint. In the categories listed below, "N" signifies the number of participants evaluable for the timepoint.
Arm/Group Title Idursulfase
Hide Arm/Group Description:
Open-label treatment with idursulfase
Overall Number of Participants Analyzed 26
Mean (Standard Deviation)
Unit of Measure: minutes
Week 1 (N=26) 153  (96)
Week 27 (N=18) 127  (23)
9.Secondary Outcome
Title Single- and Repeat-Dose Pharmacokinetics - Clearance (CL)
Hide Description Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Time Frame Weeks 1 and 27
Hide Outcome Measure Data
Hide Analysis Population Description
PK population with evaluable participants for this endpoint. In the categories listed below, "N" signifies the number of participants evaluable for the timepoint.
Arm/Group Title Idursulfase
Hide Arm/Group Description:
Open-label treatment with idursulfase
Overall Number of Participants Analyzed 26
Mean (Standard Deviation)
Unit of Measure: milliliter/minute/kilogram
Week 1 (N=26) 2.4  (0.7)
Week 27 (N=18) 4.7  (5.0)
10.Secondary Outcome
Title Single- and Repeat-Dose Pharmacokinetics - Volume of Distribution at Steady State (Vss)
Hide Description Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the apparent volume of distribution at steadystate.
Time Frame Weeks 1 and 27
Hide Outcome Measure Data
Hide Analysis Population Description
PK population with evaluable participants for this endpoint. In the categories listed below, "N" signifies the number of participants evaluable for the timepoint.
Arm/Group Title Idursulfase
Hide Arm/Group Description:
Open-label treatment with idursulfase
Overall Number of Participants Analyzed 26
Mean (Standard Deviation)
Unit of Measure: milliliter per kilogram
Week 1 (N=26) 394  (423)
Week 27 (N=18) 551  (528)
Time Frame From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Idursulfase
Hide Arm/Group Description Open-label treatment with idursulfase
All-Cause Mortality
Idursulfase
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Idursulfase
Affected / at Risk (%) # Events
Total   13/28 (46.43%)    
Blood and lymphatic system disorders   
Microcytic anaemia  1  1/28 (3.57%)  1
Gastrointestinal disorders   
Food poisoning  1  1/28 (3.57%)  1
General disorders   
Pyrexia  1  3/28 (10.71%)  6
Catheter site haematoma  1  1/28 (3.57%)  1
Irritability  1  1/28 (3.57%)  1
Oedema peripheral  1  1/28 (3.57%)  2
Infections and infestations   
Bronchopneumonia  1  3/28 (10.71%)  3
Otitis media  1  2/28 (7.14%)  2
Pneumonia  1  2/28 (7.14%)  2
Ear infection  1  1/28 (3.57%)  1
Gastrointestinal infection  1  1/28 (3.57%)  1
Respiratory tract infection  1  1/28 (3.57%)  2
Upper respiratory tract infection  1  1/28 (3.57%)  1
Viral pharyngitis  1  1/28 (3.57%)  1
Musculoskeletal and connective tissue disorders   
Muscle contracture  1  1/28 (3.57%)  1
Nervous system disorders   
Atonic seizures  1  1/28 (3.57%)  1
Respiratory, thoracic and mediastinal disorders   
Respiratory distress  1  2/28 (7.14%)  2
Asthma  1  1/28 (3.57%)  1
Bronchospasm  1  1/28 (3.57%)  1
Hypoxia  1  1/28 (3.57%)  1
Pulmonary hypertension  1  1/28 (3.57%)  1
Skin and subcutaneous tissue disorders   
Rash  1  1/28 (3.57%)  1
Skin hypertrophy  1  1/28 (3.57%)  1
Urticaria  1  1/28 (3.57%)  3
Vascular disorders   
Haematoma  1  1/28 (3.57%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3.57%
Idursulfase
Affected / at Risk (%) # Events
Total   28/28 (100.00%)    
Blood and lymphatic system disorders   
Eosinophilia  1  1/28 (3.57%)  1
Iron deficiency anaemia  1  1/28 (3.57%)  1
Splenomegaly  1  1/28 (3.57%)  1
Cardiac disorders   
Left ventricular hypertrophy  1  4/28 (14.29%)  4
Aortic valve incompetence  1  1/28 (3.57%)  1
Cardiomyopathy  1  1/28 (3.57%)  1
Cyanosis  1  1/28 (3.57%)  1
Right ventricular hypertrophy  1  1/28 (3.57%)  1
Sinus bradycardia  1  1/28 (3.57%)  1
Ventricular extrasystoles  1  1/28 (3.57%)  1
Congenital, familial and genetic disorders   
Hip dysplasia  1  1/28 (3.57%)  1
Ear and labyrinth disorders   
Deafness  1  4/28 (14.29%)  4
Hypoacusis  1  2/28 (7.14%)  2
Cerumen impaction  1  1/28 (3.57%)  2
Conductive deafness  1  1/28 (3.57%)  1
Ear pain  1  1/28 (3.57%)  1
Hearing impaired  1  1/28 (3.57%)  1
Otorrhoea  1  1/28 (3.57%)  1
Eye disorders   
Hypermetropia  1  2/28 (7.14%)  2
Conjunctivitis  1  1/28 (3.57%)  1
Gastrointestinal disorders   
Vomiting  1  10/28 (35.71%)  12
Diarrhoea  1  7/28 (25.00%)  35
Constipation  1  2/28 (7.14%)  3
Dental caries  1  2/28 (7.14%)  2
Toothache  1  2/28 (7.14%)  2
Abdominal pain  1  1/28 (3.57%)  2
Anal fissure  1  1/28 (3.57%)  2
Faeces hard  1  1/28 (3.57%)  2
Food poisoning  1  1/28 (3.57%)  1
Gingivitis  1  1/28 (3.57%)  1
Nausea  1  1/28 (3.57%)  2
Pruritus ani  1  1/28 (3.57%)  1
Stomatitis  1  1/28 (3.57%)  1
Umbilical hernia  1  1/28 (3.57%)  1
General disorders   
Pyrexia  1  25/28 (89.29%)  59
Fatigue  1  2/28 (7.14%)  2
Catheter site haematoma  1  1/28 (3.57%)  1
Catheter site haemorrhage  1  1/28 (3.57%)  1
Chest pain  1  1/28 (3.57%)  1
Irritability  1  1/28 (3.57%)  1
Malaise  1  1/28 (3.57%)  2
Oedema peripheral  1  1/28 (3.57%)  2
Infections and infestations   
Upper respiratory tract infection  1  18/28 (64.29%)  42
Respiratory tract infection  1  12/28 (42.86%)  36
Rhinitis  1  11/28 (39.29%)  20
Viral upper respiratory tract infection  1  9/28 (32.14%)  17
Otitis media acute  1  7/28 (25.00%)  10
Pharyngitis  1  7/28 (25.00%)  18
Gastroenteritis  1  6/28 (21.43%)  7
Upper respiratory tract infection bacterial  1  6/28 (21.43%)  13
Pneumonia  1  3/28 (10.71%)  3
Sinusitis  1  5/28 (17.86%)  6
Bronchitis  1  4/28 (14.29%)  4
Bronchopneumonia  1  3/28 (10.71%)  4
Otitis media  1  2/28 (7.14%)  3
Gastrointestinal infection  1  2/28 (7.14%)  2
Otitis externa  1  3/28 (10.71%)  5
Viral infection  1  3/28 (10.71%)  4
Viral pharyngitis  1  2/28 (7.14%)  2
Ear infection  1  2/28 (7.14%)  2
Gastroenteritis viral  1  2/28 (7.14%)  2
Herpes virus infection  1  2/28 (7.14%)  2
Influenza  1  2/28 (7.14%)  2
Laryngitis  1  2/28 (7.14%)  2
Nasopharyngitis  1  2/28 (7.14%)  2
Tonsillitis  1  2/28 (7.14%)  2
Abscess limb  1  1/28 (3.57%)  1
Body tinea  1  1/28 (3.57%)  1
Candidiasis  1  1/28 (3.57%)  1
Catheter site infection  1  1/28 (3.57%)  1
Herpes zoster  1  1/28 (3.57%)  1
Lice infestation  1  1/28 (3.57%)  1
Oral candidiasis  1  1/28 (3.57%)  1
Otitis media chronic  1  1/28 (3.57%)  1
Rash pustular  1  1/28 (3.57%)  1
Tinea versicolour  1  1/28 (3.57%)  1
Tonsillitis bacterial  1  1/28 (3.57%)  2
Varicella  1  1/28 (3.57%)  1
Viral diarrhoea  1  1/28 (3.57%)  2
Injury, poisoning and procedural complications   
Burns second degree  1  1/28 (3.57%)  1
Contusion  1  1/28 (3.57%)  1
Fall  1  1/28 (3.57%)  1
Head injury  1  1/28 (3.57%)  1
Limb injury  1  1/28 (3.57%)  1
Mouth injury  1  1/28 (3.57%)  1
Procedural pain  1  1/28 (3.57%)  1
Sunburn  1  1/28 (3.57%)  1
Investigations   
Hepatic enzyme abnormal  1  2/28 (7.14%)  2
Alanine aminotransferase increased  1  1/28 (3.57%)  1
Cardiac murmur  1  1/28 (3.57%)  1
Electrocardiogram repolarisation abnormality  1  1/28 (3.57%)  1
Gamma-glutamyltransferase increased  1  1/28 (3.57%)  1
Lymphocyte morphology abnormal  1  1/28 (3.57%)  1
Monocyte count decreased  1  1/28 (3.57%)  1
Metabolism and nutrition disorders   
Hypercalcaemia  1  1/28 (3.57%)  1
Hyperuricaemia  1  1/28 (3.57%)  1
Obesity  1  1/28 (3.57%)  1
Musculoskeletal and connective tissue disorders   
Muscle contracture  1  1/28 (3.57%)  1
Arthralgia  1  1/28 (3.57%)  2
Lordosis  1  1/28 (3.57%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Skin papilloma  1  1/28 (3.57%)  1
Nervous system disorders   
Tremor  1  2/28 (7.14%)  2
Atonic seizures  1  1/28 (3.57%)  1
Epilepsy  1  1/28 (3.57%)  1
Headache  1  1/28 (3.57%)  1
Hypoaesthesia  1  1/28 (3.57%)  1
Somnolence  1  1/28 (3.57%)  1
Psychiatric disorders   
Agitation  1  4/28 (14.29%)  5
Sleep disorder  1  3/28 (10.71%)  3
Bipolar disorder  1  1/28 (3.57%)  1
Crying  1  1/28 (3.57%)  1
Insomnia  1  1/28 (3.57%)  1
Learning disorder  1  1/28 (3.57%)  1
Renal and urinary disorders   
Enuresis  1  1/28 (3.57%)  1
Respiratory, thoracic and mediastinal disorders   
Cough  1  16/28 (57.14%)  45
Nasal congestion  1  6/28 (21.43%)  9
Allergic cough  1  3/28 (10.71%)  3
Asthma  1  2/28 (7.14%)  2
Rhinorrhoea  1  3/28 (10.71%)  4
Sleep apnea syndrome  1  3/28 (10.71%)  3
Bronchospasm  1  2/28 (7.14%)  3
Respiratory distress  1  2/28 (7.14%)  2
Choking  1  1/28 (3.57%)  1
Dyspnoea  1  1/28 (3.57%)  1
Hypoxia  1  1/28 (3.57%)  1
Lung infiltration  1  1/28 (3.57%)  1
Pharyngolaryngeal pain  1  1/28 (3.57%)  1
Pulmonary hypertension  1  1/28 (3.57%)  2
Respiratory disorder  1  1/28 (3.57%)  1
Skin and subcutaneous tissue disorders   
Rash  1  6/28 (21.43%)  11
Urticaria  1  4/28 (14.29%)  7
Dermatitis diaper  1  2/28 (7.14%)  3
Eczema  1  2/28 (7.14%)  2
Erythema  1  2/28 (7.14%)  2
Heat rash  1  2/28 (7.14%)  4
Petechiae  1  2/28 (7.14%)  2
Rash maculo-papular  1  2/28 (7.14%)  2
Rash papular  1  2/28 (7.14%)  2
Dermatitis  1  1/28 (3.57%)  1
Dermatitis allergic  1  1/28 (3.57%)  2
Dermatitis atopic  1  1/28 (3.57%)  1
Intertrigo  1  1/28 (3.57%)  1
Palmar-plantar erythrodysaesthesia syndrome  1  1/28 (3.57%)  1
Pruritus  1  1/28 (3.57%)  1
Rash generalised  1  1/28 (3.57%)  1
Skin hypertrophy  1  1/28 (3.57%)  1
Skin hypopigmentation  1  1/28 (3.57%)  1
Skin lesion  1  1/28 (3.57%)  1
Urticaria papular  1  1/28 (3.57%)  1
Vascular disorders   
Haematoma  1  1/28 (3.57%)  1
Haemorrhage  1  1/28 (3.57%)  1
Hyperaemia  1  1/28 (3.57%)  2
Hypertension  1  1/28 (3.57%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.1)
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: Arian Pano, MD, MPH
Organization: Shire HGT
Phone: 781-482-0875
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00607386     History of Changes
Other Study ID Numbers: HGT-ELA-038
2007-006044-22 ( EudraCT Number )
First Submitted: January 22, 2008
First Posted: February 5, 2008
Results First Submitted: September 3, 2013
Results First Posted: November 7, 2013
Last Update Posted: October 28, 2015