E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of Hunter syndrome and cognitive impairment |
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E.1.1.1 | Medical condition in easily understood language |
Hunter syndrome - Iduronate-2-Sulfatase enzyme deficiency |
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E.1.1.2 | Therapeutic area | Body processes [G] - Genetic Phenomena [G05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10056889 |
E.1.2 | Term | Mucopolysaccharidosis II |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To collect long-term safety data in pediatric patients with Hunter syndrome and cognitive impairment who are receiving intrathecal idursulfase-IT and intravenous (IV) Elaprase® enzyme replacement therapy |
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E.2.2 | Secondary objectives of the trial |
- To determine the serum pharmacokinetic (PK) profile of idursulfase when administered as intrathecal idursulfase-IT and in conjunction with Elaprase
- To determine the effect of intrathecal idursulfase-IT, given in conjunction with Elaprase, on CSF biomarkers (eg, glycosaminoglycan [GAG], heparan sulfate [HS]/dermatan sulfate [DS], GAG-degradation products, and markers of lysosomal function)
- To determine the effects of intrathecal idursulfase-IT, given in conjunction with Elaprase, on urinary GAGs and GAG-degradation products |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1 Patients must have completed all study requirements and EOS asessments for Study HGT-HIT-045 prior to enrolling in Study HGT-HIT-046 and must have no safety or medical issues that contraindicate participation.
2 The patient's parent(s) or legally authorized guardian(s) 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. Consent of the patient's parent(s) or legally authorized guardian(s) and the patient's assent, as relevant, must be obtained.
3 The patient has received and tolerated a minimum of 12 months of treatment with weekly IV infusions of Elaprase and has received 80% of the total planned infusions within the last 6 months. |
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E.4 | Principal exclusion criteria |
1 The patient is enrolled in another clinical study that involves clinical investigations or use of any investigational product (drug or device) other than the PORT-ACATH IDDD within 30 days prior to study enrollment or at any time during the study.
2 The patient is unable to comply with the protocol (eg, is unable to return for safety evaluations, or is otherwise unlikely to complete the study) as determined by the Investigator.
3 The patient has experienced an adverse reaction to study drug in Study HGT-HIT-045 that contraindicates further treatment with intrathecal idursulfase-IT.
4 The patient has a known hypersensitivity to any of the components of idursulfase-IT.
An additional exclusion criterion for patients who were previously untreated with intrathecal idursulfase-IT in Study HGT-HIT-045:
1. The patient has an opening CSF pressure upon lumbar puncture that exceeds 30.0 cm H2O. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety of intrathecal idursulfase-IT administration. Safety will be measured by AEs (by type and severity), changes in clinical laboratory testing (serum chemistry including liver function tests, hematology, urinalysis), 12-lead ECG, CSF chemistries (contingent on sample availability; cell counts, glucose, and protein), and anti-idursulfase antibodies and a tibodies having enzyme neutralizing activity in CSF and serum. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Pre-Treatment timepoints at monthly visits as defined in the protocol. |
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E.5.2 | Secondary end point(s) |
- Serum idursulfase concentration-time profiles and serum PK parameters of idursulfase, administered as intrathecal idursulfase-IT and in conjunction with Elaprase
- Change from baseline in CSF biomarkers (eg, GAG [HS/DS], GAG-degradation products, and markers of lysosomal function)
- Change from baseline in urinary GAGs and GAG-degradation products |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PK sampling in blood - several timepoints up to 36 hours following IT injection at months 19, 31, 43, 55, and 67. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study will conclude after the last patient has completed his last visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |