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An Observational Study Evaluating Anti-Idursulfase Serum Antibody Response in Hunter Syndrome Patients

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: NCT00882921
Recruitment Status : Completed
First Posted : April 17, 2009
Results First Posted : July 30, 2014
Last Update Posted : January 9, 2019
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Observational
Study Design Observational Model: Cohort;   Time Perspective: Prospective
Condition Hunter Syndrome
Intervention Biological: Idursulfase
Enrollment 26
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Elaprase® (0.5 mg/kg)
Hide Arm/Group Description [Not Specified]
Period Title: Overall Study
Started 26
Completed 15
Not Completed 11
Reason Not Completed
Death             2
Not specified             3
Lost to Follow-up             2
Termination By Investigator             3
Withdrawal Of Consent             1
Arm/Group Title Elaprase® (0.5 mg/kg)
Hide Arm/Group Description [Not Specified]
Overall Number of Baseline Participants 26
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 26 participants
12.82  (8.012)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 26 participants
<12 years 17
≥12 Years 9
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
Female
0
   0.0%
Male
26
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 26 participants
BRAZIL 6
UNITED KINGDOM 14
UNITED STATES 6
1.Primary Outcome
Title Infusion-Related Adverse Event (IRAE) Rates Between IgG Anti-idursulfase Antibody Positive (Ab+) and Anti-idursulfase IgG Antibody Negative (Ab-) Patients
Hide Description The primary analysis of how presence of antibodies affected IRAE rates was performed based on a negative binomial regression model. This was done to account for potentially differential follow-up time between antibody groups.
Time Frame Baseline to 109 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Population was defined as all enrolled patients who received any portion of a dose of Elaprase.
Arm/Group Title Idursulfase (Elaprase) 0.5 mg/kg Weekly
Hide Arm/Group Description:
Idursulfase: Patients will receive idursulfase as prescribed by their physician following locally approved prescribing information. Patients will not be provided idursulfase by Shire or the HOS.
Overall Number of Participants Analyzed 26
Measure Type: Number
Unit of Measure: IRAE/Week
Ab+ (n =13) 0.0121
Ab- (n = 13) 0.0042
Ab+ (age adjusted)(n = 13) 0.0055
Ab- (age adjusted)(n = 13) 0.0026
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Idursulfase (Elaprase) 0.5 mg/kg Weekly
Comments The groups compared are Ab+ vs Ab-
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1309
Comments [Not Specified]
Method Negative Binomial Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 2.873
Confidence Interval (2-Sided) 95%
0.731 to 11.296
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Idursulfase (Elaprase) 0.5 mg/kg Weekly
Comments The groups compared are Ab+ (age adjusted) vs Ab- (age adjusted)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2718
Comments [Not Specified]
Method Negative Binomial Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 2.082
Confidence Interval (2-Sided) 95%
0.563 to 7.706
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in uGAG Levels to 109 Weeks
Hide Description Urine GAG
Time Frame Baseline to 109 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Population was defined as all enrolled patients who received any portion of a dose of Elaprase. The primary analysis of how presence of antibodies affected IRAE rates was performed based on a negative binomial regression model. This was done to account for potentially differential follow-up time between antibody groups.
Arm/Group Title Elaprase
Hide Arm/Group Description:

Idursulfase 0.5 mg/kg Weekly

Idursulfase: Patients will receive idursulfase as prescribed by their physician following locally approved prescribing information. Patients will not be provided idursulfase by Shire or the HOS.

Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: mcg/mg
-74.07  (246.663)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Elaprase® (0.5 mg/kg)
Hide Arm/Group Description [Not Specified]
All-Cause Mortality
Elaprase® (0.5 mg/kg)
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Elaprase® (0.5 mg/kg)
Affected / at Risk (%) # Events
Total   16/26 (61.54%)    
Congenital, familial and genetic disorders   
Arnold-Chiari malformation  1/26 (3.85%)  1
Gastrointestinal disorders   
Abdominal distension  1/26 (3.85%)  1
Abdominal pain  1/26 (3.85%)  2
Dental caries  1/26 (3.85%)  1
Inguinal hernia, obstructive  1/26 (3.85%)  1
General disorders   
Hernia obstructive  1/26 (3.85%)  1
Multi-organ failure  1/26 (3.85%)  1
Pain  1/26 (3.85%)  1
Infections and infestations   
Central line infection  2/26 (7.69%)  2
Lower respiratory tract infection  3/26 (11.54%)  3
Pneumonia  1/26 (3.85%)  1
Upper respiratory tract infection  2/26 (7.69%)  2
Injury, poisoning and procedural complications   
Seroma  1/26 (3.85%)  1
Investigations   
Brain stem auditory evoked response  1/26 (3.85%)  1
Musculoskeletal and connective tissue disorders   
Cervical spinal stenosis  1/26 (3.85%)  1
Nervous system disorders   
Carpal tunnel syndrome  2/26 (7.69%)  3
Convulsion  5/26 (19.23%)  6
Grand mal convulsion  1/26 (3.85%)  1
Hydrocephalus  1/26 (3.85%)  1
Neurological decompensation  1/26 (3.85%)  1
Syringomyelia  1/26 (3.85%)  1
Psychiatric disorders   
Agitation  2/26 (7.69%)  2
Respiratory, thoracic and mediastinal disorders   
Acute respiratory failure  1/26 (3.85%)  1
Bronchial hyperreactivity  1/26 (3.85%)  1
Dysphonia  1/26 (3.85%)  1
Increased upper airway secretion  1/26 (3.85%)  1
Respiratory distress  1/26 (3.85%)  1
Respiratory failure  1/26 (3.85%)  1
Respiratory tract congestion  1/26 (3.85%)  1
Sleep apnoea syndrome  1/26 (3.85%)  1
Surgical and medical procedures   
Aortic valve replacement  1/26 (3.85%)  1
Catheterisation venous  1/26 (3.85%)  1
Gastrostomy tube insertion  1/26 (3.85%)  1
Spinal operation  1/26 (3.85%)  1
Tonsillectomy  1/26 (3.85%)  1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Elaprase® (0.5 mg/kg)
Affected / at Risk (%) # Events
Total   24/26 (92.31%)    
Ear and labyrinth disorders   
Deafness  2/26 (7.69%)  2
Ear pain  3/26 (11.54%)  9
Eye disorders   
Eye pruritus  2/26 (7.69%)  2
Eye swelling  2/26 (7.69%)  2
Gastrointestinal disorders   
Abdominal pain  4/26 (15.38%)  4
Constipation  6/26 (23.08%)  8
Diarrhoea  6/26 (23.08%)  11
Gastrooesophageal reflux disease  2/26 (7.69%)  2
Nausea  2/26 (7.69%)  2
Vomiting  6/26 (23.08%)  13
General disorders   
Adverse drug reaction  2/26 (7.69%)  5
Asthenia  2/26 (7.69%)  2
Catheter related complication  3/26 (11.54%)  7
Fatigue  3/26 (11.54%)  3
Gait disturbance  2/26 (7.69%)  2
Influenza like illness  2/26 (7.69%)  2
Infusion site extravasation  2/26 (7.69%)  5
Pain  2/26 (7.69%)  2
Pyrexia  14/26 (53.85%)  43
Immune system disorders   
Seasonal allergy  2/26 (7.69%)  2
Infections and infestations   
Balanitis candida  2/26 (7.69%)  3
Catheter site infection  2/26 (7.69%)  3
Central line infection  2/26 (7.69%)  2
Ear infection  9/26 (34.62%)  20
Gastroenteritis  4/26 (15.38%)  4
Influenza  4/26 (15.38%)  8
Lower respiratory tract infection  9/26 (34.62%)  23
Nasopharyngitis  3/26 (11.54%)  9
Oral candidiasis  3/26 (11.54%)  5
Otitis externa  4/26 (15.38%)  5
Otitis media  3/26 (11.54%)  4
Pharyngitis  2/26 (7.69%)  4
Staphylococcal infection  2/26 (7.69%)  2
Upper respiratory tract infection  12/26 (46.15%)  25
Injury, poisoning and procedural complications   
Contusion  3/26 (11.54%)  4
Fall  9/26 (34.62%)  14
Post procedural haemorrhage  2/26 (7.69%)  2
Investigations   
Body temperature increased  2/26 (7.69%)  5
Musculoskeletal and connective tissue disorders   
Arthralgia  7/26 (26.92%)  10
Back pain  5/26 (19.23%)  5
Mobility decreased  2/26 (7.69%)  2
Musculoskeletal pain  3/26 (11.54%)  3
Musculoskeletal stiffness  2/26 (7.69%)  2
Pain in extremity  4/26 (15.38%)  7
Nervous system disorders   
Carpal tunnel syndrome  2/26 (7.69%)  2
Convulsion  6/26 (23.08%)  53
Dizziness  3/26 (11.54%)  4
Grand mal convulsion  2/26 (7.69%)  7
Headache  6/26 (23.08%)  31
Paraesthesia  2/26 (7.69%)  4
Petit mal epilepsy  5/26 (19.23%)  6
Poor quality sleep  2/26 (7.69%)  2
Somnolence  2/26 (7.69%)  2
Psychiatric disorders   
Agitation  2/26 (7.69%)  2
Insomnia  3/26 (11.54%)  4
Respiratory, thoracic and mediastinal disorders   
Choking  2/26 (7.69%)  2
Cough  11/26 (42.31%)  25
Epistaxis  2/26 (7.69%)  6
Obstructive airways disorder  2/26 (7.69%)  2
Oropharyngeal pain  6/26 (23.08%)  9
Productive cough  3/26 (11.54%)  3
Rales  2/26 (7.69%)  4
Rhinorrhoea  5/26 (19.23%)  9
Sleep apnoea syndrome  3/26 (11.54%)  3
Upper respiratory tract congestion  2/26 (7.69%)  2
Wheezing  2/26 (7.69%)  3
Skin and subcutaneous tissue disorders   
Rash  6/26 (23.08%)  6
Skin chapped  2/26 (7.69%)  2
Surgical and medical procedures   
Central venous catheter removal  2/26 (7.69%)  2
Vascular disorders   
Flushing  2/26 (7.69%)  5
Hypertension  2/26 (7.69%)  4
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
Organization: Shire
Phone: +1 866 842 5335
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00882921     History of Changes
Other Study ID Numbers: HGT-ELA-042
First Submitted: April 16, 2009
First Posted: April 17, 2009
Results First Submitted: June 23, 2014
Results First Posted: July 30, 2014
Last Update Posted: January 9, 2019