Trial Outcomes & Findings for An Observational Study Evaluating Anti-Idursulfase Serum Antibody Response in Hunter Syndrome Patients (NCT NCT00882921)
NCT ID: NCT00882921
Last Updated: 2021-06-08
Results Overview
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.
Recruitment status
COMPLETED
Target enrollment
26 participants
Primary outcome timeframe
Baseline to 109 Weeks
Results posted on
2021-06-08
Participant Flow
Participant milestones
| Measure |
Elaprase® (0.5 mg/kg)
|
|---|---|
|
Overall Study
STARTED
|
26
|
|
Overall Study
COMPLETED
|
15
|
|
Overall Study
NOT COMPLETED
|
11
|
Reasons for withdrawal
| Measure |
Elaprase® (0.5 mg/kg)
|
|---|---|
|
Overall Study
Death
|
2
|
|
Overall Study
Other
|
3
|
|
Overall Study
Lost to Follow-up
|
2
|
|
Overall Study
Termination By Investigator
|
3
|
|
Overall Study
Withdrawal Of Consent
|
1
|
Baseline Characteristics
An Observational Study Evaluating Anti-Idursulfase Serum Antibody Response in Hunter Syndrome Patients
Baseline characteristics by cohort
| Measure |
Elaprase® (0.5 mg/kg)
n=26 Participants
|
|---|---|
|
Age, Continuous
|
12.82 Years
STANDARD_DEVIATION 8.012 • n=5 Participants
|
|
Age, Customized
<12 years
|
17 Participants
n=5 Participants
|
|
Age, Customized
≥12 Years
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=5 Participants
|
|
Region of Enrollment
BRAZIL
|
6 Participants
n=5 Participants
|
|
Region of Enrollment
UNITED KINGDOM
|
14 Participants
n=5 Participants
|
|
Region of Enrollment
UNITED STATES
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to 109 WeeksPopulation: 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.
Outcome measures
| Measure |
Idursulfase (Elaprase) 0.5 mg/kg Weekly
n=26 Participants
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.
|
|---|---|
|
Infusion-Related Adverse Event (IRAE) Rates Between IgG Anti-idursulfase Antibody Positive (Ab+) and Anti-idursulfase IgG Antibody Negative (Ab-) Patients
Ab+ (n =13)
|
0.0121 IRAE/Week
|
|
Infusion-Related Adverse Event (IRAE) Rates Between IgG Anti-idursulfase Antibody Positive (Ab+) and Anti-idursulfase IgG Antibody Negative (Ab-) Patients
Ab- (n = 13)
|
0.0042 IRAE/Week
|
|
Infusion-Related Adverse Event (IRAE) Rates Between IgG Anti-idursulfase Antibody Positive (Ab+) and Anti-idursulfase IgG Antibody Negative (Ab-) Patients
Ab+ (age adjusted)(n = 13)
|
0.0055 IRAE/Week
|
|
Infusion-Related Adverse Event (IRAE) Rates Between IgG Anti-idursulfase Antibody Positive (Ab+) and Anti-idursulfase IgG Antibody Negative (Ab-) Patients
Ab- (age adjusted)(n = 13)
|
0.0026 IRAE/Week
|
SECONDARY outcome
Timeframe: Baseline to 109 WeeksPopulation: 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.
Urine GAG
Outcome measures
| Measure |
Idursulfase (Elaprase) 0.5 mg/kg Weekly
n=15 Participants
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.
|
|---|---|
|
Change From Baseline in uGAG Levels to 109 Weeks
|
-74.07 mcg/mg
Standard Deviation 246.663
|
Adverse Events
Elaprase® (0.5 mg/kg)
Serious events: 16 serious events
Other events: 24 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Elaprase® (0.5 mg/kg)
n=26 participants at risk
|
|---|---|
|
Congenital, familial and genetic disorders
Arnold-Chiari malformation
|
3.8%
1/26 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal distension
|
3.8%
1/26 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
3.8%
1/26 • Number of events 2
|
|
Gastrointestinal disorders
Dental caries
|
3.8%
1/26 • Number of events 1
|
|
Gastrointestinal disorders
Inguinal hernia, obstructive
|
3.8%
1/26 • Number of events 1
|
|
General disorders
Hernia obstructive
|
3.8%
1/26 • Number of events 1
|
|
General disorders
Multi-organ failure
|
3.8%
1/26 • Number of events 1
|
|
General disorders
Pain
|
3.8%
1/26 • Number of events 1
|
|
Infections and infestations
Central line infection
|
7.7%
2/26 • Number of events 2
|
|
Infections and infestations
Lower respiratory tract infection
|
11.5%
3/26 • Number of events 3
|
|
Infections and infestations
Pneumonia
|
3.8%
1/26 • Number of events 1
|
|
Infections and infestations
Upper respiratory tract infection
|
7.7%
2/26 • Number of events 2
|
|
Injury, poisoning and procedural complications
Seroma
|
3.8%
1/26 • Number of events 1
|
|
Investigations
Brain stem auditory evoked response
|
3.8%
1/26 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Cervical spinal stenosis
|
3.8%
1/26 • Number of events 1
|
|
Nervous system disorders
Carpal tunnel syndrome
|
7.7%
2/26 • Number of events 3
|
|
Nervous system disorders
Convulsion
|
19.2%
5/26 • Number of events 6
|
|
Nervous system disorders
Grand mal convulsion
|
3.8%
1/26 • Number of events 1
|
|
Nervous system disorders
Hydrocephalus
|
3.8%
1/26 • Number of events 1
|
|
Nervous system disorders
Neurological decompensation
|
3.8%
1/26 • Number of events 1
|
|
Nervous system disorders
Syringomyelia
|
3.8%
1/26 • Number of events 1
|
|
Psychiatric disorders
Agitation
|
7.7%
2/26 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
3.8%
1/26 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity
|
3.8%
1/26 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
3.8%
1/26 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Increased upper airway secretion
|
3.8%
1/26 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
3.8%
1/26 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
3.8%
1/26 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
3.8%
1/26 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
3.8%
1/26 • Number of events 1
|
|
Surgical and medical procedures
Aortic valve replacement
|
3.8%
1/26 • Number of events 1
|
|
Surgical and medical procedures
Catheterisation venous
|
3.8%
1/26 • Number of events 1
|
|
Surgical and medical procedures
Gastrostomy tube insertion
|
3.8%
1/26 • Number of events 1
|
|
Surgical and medical procedures
Spinal operation
|
3.8%
1/26 • Number of events 1
|
|
Surgical and medical procedures
Tonsillectomy
|
3.8%
1/26 • Number of events 1
|
Other adverse events
| Measure |
Elaprase® (0.5 mg/kg)
n=26 participants at risk
|
|---|---|
|
Ear and labyrinth disorders
Deafness
|
7.7%
2/26 • Number of events 2
|
|
Ear and labyrinth disorders
Ear pain
|
11.5%
3/26 • Number of events 9
|
|
Eye disorders
Eye pruritus
|
7.7%
2/26 • Number of events 2
|
|
Eye disorders
Eye swelling
|
7.7%
2/26 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal pain
|
15.4%
4/26 • Number of events 4
|
|
Gastrointestinal disorders
Constipation
|
23.1%
6/26 • Number of events 8
|
|
Gastrointestinal disorders
Diarrhoea
|
23.1%
6/26 • Number of events 11
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
7.7%
2/26 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
7.7%
2/26 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
23.1%
6/26 • Number of events 13
|
|
General disorders
Adverse drug reaction
|
7.7%
2/26 • Number of events 5
|
|
General disorders
Asthenia
|
7.7%
2/26 • Number of events 2
|
|
General disorders
Catheter related complication
|
11.5%
3/26 • Number of events 7
|
|
General disorders
Fatigue
|
11.5%
3/26 • Number of events 3
|
|
General disorders
Gait disturbance
|
7.7%
2/26 • Number of events 2
|
|
General disorders
Influenza like illness
|
7.7%
2/26 • Number of events 2
|
|
General disorders
Infusion site extravasation
|
7.7%
2/26 • Number of events 5
|
|
General disorders
Pain
|
7.7%
2/26 • Number of events 2
|
|
General disorders
Pyrexia
|
53.8%
14/26 • Number of events 43
|
|
Immune system disorders
Seasonal allergy
|
7.7%
2/26 • Number of events 2
|
|
Infections and infestations
Balanitis candida
|
7.7%
2/26 • Number of events 3
|
|
Infections and infestations
Catheter site infection
|
7.7%
2/26 • Number of events 3
|
|
Infections and infestations
Central line infection
|
7.7%
2/26 • Number of events 2
|
|
Infections and infestations
Ear infection
|
34.6%
9/26 • Number of events 20
|
|
Infections and infestations
Gastroenteritis
|
15.4%
4/26 • Number of events 4
|
|
Infections and infestations
Influenza
|
15.4%
4/26 • Number of events 8
|
|
Infections and infestations
Lower respiratory tract infection
|
34.6%
9/26 • Number of events 23
|
|
Infections and infestations
Nasopharyngitis
|
11.5%
3/26 • Number of events 9
|
|
Infections and infestations
Oral candidiasis
|
11.5%
3/26 • Number of events 5
|
|
Infections and infestations
Otitis externa
|
15.4%
4/26 • Number of events 5
|
|
Infections and infestations
Otitis media
|
11.5%
3/26 • Number of events 4
|
|
Infections and infestations
Pharyngitis
|
7.7%
2/26 • Number of events 4
|
|
Infections and infestations
Staphylococcal infection
|
7.7%
2/26 • Number of events 2
|
|
Infections and infestations
Upper respiratory tract infection
|
46.2%
12/26 • Number of events 25
|
|
Injury, poisoning and procedural complications
Contusion
|
11.5%
3/26 • Number of events 4
|
|
Injury, poisoning and procedural complications
Fall
|
34.6%
9/26 • Number of events 14
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
7.7%
2/26 • Number of events 2
|
|
Investigations
Body temperature increased
|
7.7%
2/26 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
26.9%
7/26 • Number of events 10
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
19.2%
5/26 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Mobility decreased
|
7.7%
2/26 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
11.5%
3/26 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
7.7%
2/26 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
15.4%
4/26 • Number of events 7
|
|
Nervous system disorders
Carpal tunnel syndrome
|
7.7%
2/26 • Number of events 2
|
|
Nervous system disorders
Convulsion
|
23.1%
6/26 • Number of events 53
|
|
Nervous system disorders
Dizziness
|
11.5%
3/26 • Number of events 4
|
|
Nervous system disorders
Grand mal convulsion
|
7.7%
2/26 • Number of events 7
|
|
Nervous system disorders
Headache
|
23.1%
6/26 • Number of events 31
|
|
Nervous system disorders
Paraesthesia
|
7.7%
2/26 • Number of events 4
|
|
Nervous system disorders
Petit mal epilepsy
|
19.2%
5/26 • Number of events 6
|
|
Nervous system disorders
Poor quality sleep
|
7.7%
2/26 • Number of events 2
|
|
Nervous system disorders
Somnolence
|
7.7%
2/26 • Number of events 2
|
|
Psychiatric disorders
Agitation
|
7.7%
2/26 • Number of events 2
|
|
Psychiatric disorders
Insomnia
|
11.5%
3/26 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Choking
|
7.7%
2/26 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
42.3%
11/26 • Number of events 25
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
7.7%
2/26 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Obstructive airways disorder
|
7.7%
2/26 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
23.1%
6/26 • Number of events 9
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
11.5%
3/26 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Rales
|
7.7%
2/26 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
19.2%
5/26 • Number of events 9
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
11.5%
3/26 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract congestion
|
7.7%
2/26 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
7.7%
2/26 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Rash
|
23.1%
6/26 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
Skin chapped
|
7.7%
2/26 • Number of events 2
|
|
Surgical and medical procedures
Central venous catheter removal
|
7.7%
2/26 • Number of events 2
|
|
Vascular disorders
Flushing
|
7.7%
2/26 • Number of events 5
|
|
Vascular disorders
Hypertension
|
7.7%
2/26 • Number of events 4
|
Additional Information
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