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 defficiency |
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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 | 20.1 |
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], including heparan sulfate [HS]/dermatan sulfate [DS]
- To determine the effects of intrathecal idursulfase-IT, given in conjunction with Elaprase, on urinary GAGs
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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 representative(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 representative(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-A-CATH 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.
5. The patient has any known or suspected hypersensitivity to anesthesia or is thought to be at an unacceptably high risk for anesthesia due to airway compromise or other conditions.
6. The patient has a condition that is contraindicated as described in the SOPH-A-PORT Mini S IDDD Instructions for Use, including:
a. The patient has had, or may have, an allergic reaction to the materials of construction of the SOPH-A-PORT Mini S device
b. The patient’s body size is too small to support the size of the SOPH-A-PORT Mini S
Access Port, as judged by the Investigator
c. The patient’s drug therapy requires substances known to be incompatible with the
materials of construction
d. The patient has a known or suspected local or general infection
e. The patient is at risk of abnormal bleeding due to a medical condition or therapy
f. The patient has one or more spinal abnormalities that could complicate safe implantation or fixation
g. The patient has a functioning CSF shunt device
h. The patient has shown an intolerance to an implanted device
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 antibodies 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]
- Change from baseline in urinary GAGs |
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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 week 3 and 23 (initial treatment phase) and at months 19, 31 and 43 (extended treatment phase). |
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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 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
United Kingdom |
United States |
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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.8.9.1 | In the Member State concerned years | 14 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 14 |
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 |