Hunter Syndrome
Conditions
Keywords
MPS 2, MPSII, hunter's disease treatment, enzyme replacement therapy, hunter's disease, iduronate 2 sulfatase, mps diagnosis, mps symptoms, iduronate sulfatase, MPS II treatment, chronic ear infection, hunters syndrome, mps ii therapy, MPS2, hunter's syndrome, Hunter syndrome, elaprase, lysosomal storage disease, hunter syndrome therapy, mps society, hunter syndrome treatment, hunter's syndrome treatment, mucopolysaccharides, mps ii, idursulfase, hunters disease, enlarged adenoids, ert treatment, hunter disease, lysosomal storage disorder
Brief summary
The objective of this study is to evaluate the effect of anti-idursulfase antibodies on idursulfase safety (measured by infusion related adverse events) between patients who develop anti-idursulfase antibodies and patients who do not after long-term idursulfase enzyme replacement therapy (ERT).
Detailed description
This study is being conducted to satisfy post-marketing commitments to monitor anti-idursulfase antibody development in Hunter syndrome patients after long-term idursulfase enzyme replacement therapy. The study will be conducted as a sub-study within the Hunter Outcome Survey (HOS). Hunter syndrome patients in the HOS who have previously received idursulfase as well as treatment-naive patients who will begin idursulfase treatment within 30 days of study enrollment will be included.
Interventions
BIOLOGICALIdursulfase
Patients received idursulfase as prescribed by their physician following locally approved prescribing information. Patients will not be provided idursulfase by Shire Human Genetic Therapies, Inc. or the HOS.
Sponsors
Shire
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
5 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients must meet all of the following criteria to be considered eligible for enrollment: * The patient is male and enrolled in the HOS (i.e., meets the entry criteria of a documented diagnosis of Hunter syndrome) * The patient is ≥ 5 years-old * The patient is on idursulfase treatment or scheduled to begin idursulfase treatment within 30 days of study enrollment * The patient, patient's parent(s), or patient's legally authorized guardian must have voluntarily signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient, patient's parent(s), or patient's legally authorized guardian.
Exclusion criteria
Patients who meet any of the following criteria are not eligible for this study: * The patient has received biologic/ERT products other than idursulfase, or other investigational product(s) for any reason within 30 days prior to study entry. * The patient has a life expectancy of \< 2 years * The patient is unable to comply with the protocol, e.g., has a clinically relevant medical condition making implementation of the protocol difficult; has an uncooperative attitude; is unable to return for safety evaluations; or is otherwise unlikely to complete the study, as determined by the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Infusion-Related Adverse Event (IRAE) Rates Between IgG Anti-idursulfase Antibody Positive (Ab+) and Anti-idursulfase IgG Antibody Negative (Ab-) Patients | Baseline to 109 Weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in uGAG Levels to 109 Weeks | Baseline to 109 Weeks | Urine GAG |
Countries
Brazil, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Elaprase® (0.5 mg/kg) | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Other | 3 |
| Overall Study | Termination By Investigator | 3 |
| Overall Study | Withdrawal Of Consent | 1 |
Baseline characteristics
| Characteristic | Elaprase® (0.5 mg/kg) |
|---|---|
| Age, Continuous | 12.82 Years STANDARD_DEVIATION 8.012 |
| Age, Customized <12 years | 17 Participants |
| Age, Customized ≥12 Years | 9 Participants |
| Region of Enrollment BRAZIL | 6 Participants |
| Region of Enrollment UNITED KINGDOM | 14 Participants |
| Region of Enrollment UNITED STATES | 6 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 24 / 26 |
| serious Total, serious adverse events | 16 / 26 |
Outcome results
Primary
Infusion-Related Adverse Event (IRAE) Rates Between IgG Anti-idursulfase Antibody Positive (Ab+) and Anti-idursulfase IgG Antibody Negative (Ab-) Patients
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
Population: The Safety Population was defined as all enrolled patients who received any portion of a dose of Elaprase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Idursulfase (Elaprase) 0.5 mg/kg Weekly | 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 |
| Idursulfase (Elaprase) 0.5 mg/kg Weekly | 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 |
| Idursulfase (Elaprase) 0.5 mg/kg Weekly | 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 |
| Idursulfase (Elaprase) 0.5 mg/kg Weekly | 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 |
Comparison: The groups compared are Ab+ vs Ab-p-value: 0.130995% CI: [0.731, 11.296]Negative Binomial Model
Comparison: The groups compared are Ab+ (age adjusted) vs Ab- (age adjusted)p-value: 0.271895% CI: [0.563, 7.706]Negative Binomial Model
Secondary
Change From Baseline in uGAG Levels to 109 Weeks
Urine GAG
Time frame: Baseline to 109 Weeks
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Idursulfase (Elaprase) 0.5 mg/kg Weekly | Change From Baseline in uGAG Levels to 109 Weeks | -74.07 mcg/mg | Standard Deviation 246.663 |